The Magpies are two points from safety with just four games left to play, and they face an in-form Liverpool side who are on a six-game unbeaten run in all competitions.
After an inconsistent start to his career as Liverpool manager, Jurgen Klopp is enjoying a run of wins as his team have recorded victories in their last four games in all competitions.
The hope of playing Champions League football next season is a reality, but that is largely down to their progression into the semi-finals of the Europa League.
Should the Merseyside outfit win the tournament then they will be handed a spot in next season's elite competition regardless of whether or not they finish in the top four of the league.
In the Premier League, Liverpool reside seventh, six points behind fourth-placed Arsenal with five games left to play, and they are five points adrift of arch rivals Manchester United.
The Reds made headlines for their dramatic comeback win over Borussia Dortmund in the quarter-finals of the Europa League last week, and they have not slowed down since.
In a much-changed side, Klopp's team managed to earn a 2-1 victory away at Bournemouth, and they also claimed the bragging rights by convincingly beating Merseyside rivals Everton.
Roberto Martinez's team have not been in the finest form of late, but Liverpool impressed with a solid performance, which resulted in a 4-0 victory thanks to goals from Divock Origi, Mamadou Sakho, Daniel Sturridge and Philippe Coutinho.
Merseyside derbies are traditionally fierce encounters, but the last 20 minutes or so turned into somewhat of an exhibition match at Anfield as Liverpool were completely dominant and Everton trudged along with 10 men following Ramiro Funes Mori's sending-off.
Despite the Reds' decent form, they have only kept one clean sheet in their last eight games in all competitions having conceded 11 goals in that time.
Liverpool fans have fully taken to Klopp, who replaced Brendan Rodgers as manager in October, but many hold a fondness for Benitez, who will return to Anfield for the first time since taking over at Newcastle last month.
Recent form: WLDWWW
Recent form (all competitions): LDDWWW
Benitez's focus will be on trying to retain Newcastle's Premier League status with just four games left to go, but considering his past with Liverpool, the Spaniard will be looking forward to returning to Anfield.
The 56-year-old spent six years in charge of the Merseyside outfit, guiding them to their fifth European title and an FA Cup final win.
The Liverpool fans have remained fond of Benitez and he maintains a close affinity to the city given that his wife and children still live on Merseyside.
He has a job at hand, though, as the Magpies are two points off safety and could do with winning their remaining four games to ensure that they still have a place in the top flight.
It was a tough start for Benitez, who has signed a three-year deal but has the option to leave in the summer if the club get relegated, as he failed to guide the team to a win in his first four fixtures.
Newcastle lost to league leaders Leicester City, drew with Sunderland and lost to both Norwich City and Southampton, but they have found some form having gone unbeaten in their last two games.
A possible turning point came last week when they earned a 3-0 win over Swansea City at St James' Park.
Newcastle would have taken the point before the game, but in the end, it was unfortunate for the North-East outfit not to come away with maximum points and climb out of the relegation zone.
The Magpies have another chance against Liverpool, but they have a poor away record this season having won just two of their 17 fixtures on the road.
Recent form: LDLLWD
Divock Origi, who has scored five goals in his last five appearances, will be missing from the Liverpool squad this weekend after he was stretchered off during his side's Merseyside win over Everton on Wednesday evening.
Klopp said after the game that the striker did not break his ankle, but he may have suffered ligament damage, which could keep him out of action for a significant period of time.
Benitez may not want to change too much with regards to his team selection as they have managed to win and draw their last two games.
Ayoze Perez replaced Georginio Wijnaldum in the lineup against Man City on Tuesday, but the latter may come back into the fold against Liverpool.
Liverpool possible starting lineup:
Mignolet; Clyne, Lovren, Sakho, Moreno; Allen, Milner; Lallana, Coutinho, Firmino; Sturridge
Newcastle United possible starting lineup:
Darlow; Anita, Mbemba, Lascelles, Dummett; Townsend, Tiote, Colback, Sissoko; Wijnaldum, Cisse
Head To Head
Newcastle have had some favourable results against Liverpool in recent years, and one of those came earlier this season when they earned a 2-0 victory at St James' Park.
Georginio Wijnaldum scored the winning goal on that day and they were helped along by an own goal from Martin Skrtel in the 69th minute.
The last time that these two sides met at Anfield was on April 13 last year and it was Liverpool who claimed a 2-0 win thanks to goals from Raheem Sterling and Joe Allen.
The past five meetings have resulted in two wins apiece and a 2-2 draw.
We say: Liverpool 2-1 Newcastle United
Liverpool are in a rich vein of form having won their last four games on the trot, and their dominant performance against Everton will give them confidence ahead of Saturday's visit of Newcastle. The Reds have scored 14 goals in that time and will feel that they can add to their tally against the Magpies. Despite Liverpool's form, they could face a sterner test against Newcastle as the North-East outfit are fighting for their lives. It should result in a win for the home side, though.