The two sides are meeting for the first time ever, with Liverpool second in Group E while Genk are bottom having only accrued one point from their opening two games.
It has been a topsy-turvy start to Liverpool's sixth European Cup/Champions League defence, with defeat in Naples on matchday one being followed by a remarkable game against Red Bull Salzburg at Anfield.
The Reds seemed to be cruising after scoring three goals in the opening 36 minutes, only for Salzburg to pull off the type of comeback their hosts have become renowned for by restoring parity on the hour mark.
Mohamed Salah's winner 21 minutes from time was greeted with huge relief around the stadium, particularly considering it was Liverpool's home form which carried them through the group stages en route to the title last season.
Indeed, Jurgen Klopp's side travel to Belgium looking to end a run of four successive away defeats at this stage of the competition, while a 7-0 drubbing of Maribor in 2017 is their only win in their last 10 such games.
Of course, there has been away glory in Europe further down the line having reached the last two finals, but they will hope to make their progress to those latter stages easier this time around with victory on Wednesday night.
It is a fixture most would expect them to win, but it is perhaps made more difficult by the games that surround it; Liverpool faced bitter rivals Manchester United just three days ago, while Tottenham Hotspur, Arsenal and Manchester City are to come in three of their next five outings.
Klopp will certainly want a response from Sunday's 1-1 draw at Old Trafford, a result which in the context of history looks decent but one which United would have been much happier with had it been offered before the start of the game.
Adam Lallana's 85th-minute equaliser at least ensured Liverpool avoided defeat, but it was the level of performance which was most disappointing rather than the fact they failed to equal the all-time English top-flight record of 18 successive victories at the home of their biggest enemies.
Liverpool's previously-perfect start means that they still boast a six-point lead at the top of the Premier League table, though, and with their two main Group E rivals facing off in the other game on Wednesday night they will hope to rise to the top of their Champions League standings too.
Anything other than victory over Genk would raise eyebrows, with the Belgian champions having played a Champions League-record 14 matches without ever winning in the competition proper.
A 6-2 hammering at the hands of Salzburg on matchday one got their campaign off to an inauspicious start, but there was a vast improvement on matchday two as they held on for a spirited goalless draw against Napoli.
That stalemate was only the second time in their last 32 European outings that Genk have failed to find the back of the net, so they may feel confident of getting at a Liverpool defence which has been uncharacteristically leaky in Europe so far this season, conceding five goals in their two games.
There is more cause for optimism for Genk when it comes to their home form, having gone six Champions League games unbeaten in front of their own fans including qualifiers - a run which stretches back to 2007 - and having lost only one of their last 17 home European outings.
Domestically things have not gone as well for the defending champions so far, sitting sixth with 12 points fewer than at the same stage of last season following Saturday's defeat to rivals Standard Liege.
Genk Champions League form: LD
Genk form (all competitions): LWWDWL
Liverpool Champions League form: LW
Liverpool form (all competitions): WWWWWD
Liverpool's major fitness concern surrounds Salah, who picked up an ankle injury against Leicester City before the international break and subsequently missed Sunday's trip to Old Trafford.
The fact that his shirt had been hung up in the dressing room was a piece of subterfuge from the Reds, but also suggests that he is not too far from a return and his inclusion in the travelling party strongly hints that he is ready to feature in this match.
Should Salah fall short then he will likely be again replaced by Divock Origi, who spent nine years in Genk's youth system before joining Lille in 2010.
Alisson Becker is now back fit after starting against United, but Joel Latip suffered a flare-up of his knee injury after that match and has not travelled with the squad to Belgium.
There is a chance that Klopp could use this game to make changes with one eye on the matches coming up, and if that is the case then the likes of Alex Oxlade-Chamberlain, Naby Keita and Sunday's hero Adam Lallana are among those hoping for a start.
Genk possible starting lineup:
Coucke; Maehle, Lucumi, Dewaest, Uronen; Heynen, Hagi, Berge; Ito, Samatta, Bongonda
Liverpool possible starting lineup:
Alisson; Gomez, Lovren, Van Dijk, Robertson; Milner, Fabinho, Wijnaldum; Salah, Firmino, Mane
We say: Genk 0-3 Liverpool
Genk may have a solid home record in Europe recently, but their goal lived a charmed life in the draw with Napoli and Liverpool's attack looks well equipped to break down their defence. It has been a while since the Reds claimed an away group-stage win in this competition, but we are backing them to do exactly that here, and in quite comfortable fashion too.