The Reds stormed to a 5-0 victory when the sides met in the first knockout round last year, scoring all of their goals in a dominant first-leg display in Portugal, and they are strong favourites to progress through 13 months on.
Like that clash with Porto last year, Liverpool are once again balancing European and domestic commitments as we enter the business end of the season. Unlike last season, though, the Reds are fighting for far more than fourth place in the Premier League.
Jurgen Klopp's side returned to the top of the table with Friday's 3-1 win at Southampton, once again getting the job done in a potential banana skin fixture despite not being anywhere near their best for large parts.
Liverpool may not be considered title favourites, with Manchester City just two points further back and boasting a game in hand, but finishing second will feel like a big disappointment should they be pipped to the post.
Reaching last season's Champions League final was a massive achievement for Liverpool, who followed up their comfortable last-16 win over Porto with aggregate victories over Man City and Roma, before losing 3-1 to a Gareth Bale-inspired Real Madrid in Kiev.
It can be argued that the Premier League takes priority for now, but Klopp's men are strong favourites to overcome Porto in this quarter-final and the field will then be wide open. For all the talk of Man City being on course for a quadruple, Liverpool can themselves make this one of the most famous seasons in their history by winning a European and league double.
Liverpool may have been handed a favourable tie, dodging the likes of Barcelona, Juventus and three of their domestic rivals, though it can be argued that they deserved to pick the weakest remaining side as they faced behemoths Bayern Munich in the previous round.
The Reds won that match 3-1 on aggregate following a goalless first leg at Anfield, and they will now fancy their chances of booking a place in the semis. From their last five quarter-final appearances in the Champions League, between 2004 and 2018, they have progressed on four occasions, only falling short against Chelsea in 2008-09.
Despite being accused of showing title nerves in recent weeks, Liverpool have won four Premier League games in a row - five out of five in all competitions, including that memorable win at Bayern - and they now have a big chance to keep their momentum going while at the same time laying down a marker as the finish line draws into sight.
Recent form in Champions League: WLLWDW
Recent form (all competitions): DWWWWW
Porto are also involved in a tight title race in their domestic league, sitting three points better off than second-placed Benfica, who play their game in hand against Feirense on Sunday evening.
The Dragons can be forgiven for taking their eye off the ball for the time being, though, as they are seeking a place in the last four of UEFA's showpiece competition for the first time since 2003-04 when they lifted the trophy under Jose Mourinho.
Their only two victories in seven previous quarter-final appearances came in the seasons when they were crowned European champions, and they do not boast the best of records against English sides - especially on English soil.
Porto have lost five of their eight two-legged ties against Premier League opposition, including defeats in each of the last five since Mourinho's side eliminated Manchester United en route to their famous success in 2004.
Sergio Conceicao will be hoping for his own 'knee-slide moment', made famous by Mourinho at Old Trafford 15 years ago, when his side make the trip to Merseyside on Tuesday.
On the back of a good run of form, winning eight of their last 10 matches in all competitions, Conceicao will be hoping that his side can give a better account of themselves than last season when collapsing on home soil to Liverpool.
Taking that goalless second-leg draw against Liverpool into account, the Portuguese giants have failed to win any of their last 12 away knockout games in the Champions League since a 1-0 victory at Deportivo La Coruna back in May 2004.
A 2-1 loss to Roma in this season's last 16 did not stop them from battling through, however, as they produced a much-improved display in the second leg on home soil to win 3-1 after extra time, scoring what proved to be the winner three minutes from the end via an Alex Telles penalty.
Liverpool will provide a tougher test than Roma, who simply did not turn up in that second leg, but Porto have a superb European record this season and they will be desperate to avenge 2017-18's horrific first-leg showing. Underdogs they may be, yet they should not be entirely written off.
Recent form in Champions League: WWWWLW
Recent form (all competitions): WWWWDW
Liverpool will be without one of their key men on Tuesday as left-back Andy Robertson picked up a late booking at the Allianz Arena to rule him out of the first leg against Porto.
The Reds, while not taking Porto lightly, will surely see this as a chance to make a few changes ahead of a gruelling schedule.
Georginio Wijnaldum has been used heavily over the last eight months and is in need of a rest, potentially giving Fabinho a chance to impress in a midfield three alongside Jordan Henderson and Naby Keita.
Porto head into this match on the back of a derby win over city rivals Boavista, meanwhile, and Conceicao was able to bring off key trio Jesus Manuel Corona, Tiquinho and Danilo Pereira with this game in mind.
There could be some bad news for Conceicao, though, as Telles picked up an injury while scoring a penalty last week and missed the derby clash with Boavista, but he is expected to be back in time for this midweek trip to Anfield.
Striker Vincent Aboubakar will play no part after rupturing his cruciate ligament earlier in the season, though it is in defence where the visitors have a particular headache.
As well as Telles's fitness concerns, experienced centre-back Pepe is suspended for the first leg, as is the influential Hector Herrera further up the field, possibly leaving them with just four fit and available defenders.
Further up the field, striker Moussa Marega is looking to become just the fourth different player in Champions League history to score in seven successive matches in the competition.
Liverpool possible starting lineup:
Alisson; Alexander-Arnold, Matip, Van Dijk, Milner; Fabinho, Henderson, Keita; Salah, Firmino, Mane
Porto possible starting lineup:
Casillas; Militao, Felipe, Leite, Telles; Corona, Danilo, Otavio, Brahimi; Marega, Soares
Head To Head
Liverpool have never lost a European match against Porto in six previous encounters.
Porto have never faced an opponent more without winning in the Champions League than Liverpool (four games), also failing in four matches against Zenit St Petersburg and Juventus.
We say: Liverpool 2-0 Porto
Porto are winless in 18 away trips to England and they have an underwhelming record in the knockout rounds of the competition. Keeping the tie alive ahead of the return match at the Estadio do Dragao in a little over a week's time will be the aim, but Liverpool will have other ideas and will be keen to take a commanding lead with them to Portugal.