In recent seasons, this fixture has gone along-way to deciding the destination of the Premier League title, with no one else claiming the crown since 2017.
Right now though, these two are 13 points apart and, by kick off, Liverpool could find themselves as low as 16th in the table.
Last weekend, the Reds’ put in one of the better performances of the season but still lost, beaten 3-2 by Arsenal.
Darwin Núñez and Roberto Firmino both bagged equaliser in North London, but a late penalty saw the league-leaders to victory.
This means Jürgen Klopp’s team have won just two league matches this season, the club’s fewest after eight games for a decade.
In contrast, Manchester City are still unbeaten, winning seven of nine outings, scoring 33 times already.
Last weekend, João Cancelo, Phil Foden, Riyāḍ Maḥrez and, of course, Elring Braut Håland all netted in a 4-0 drubbing of Southampton.
But, having drawn at both St James’ Park and Villa Park, Pep Guardiola’s team are still on point off the pace.
In the Champions League meanwhile, both can, almost, start planning for the knockout stages.
The Citizens have qualified, following Tuesday’s goalless draw with København; Maḥrez missed a penalty and Sergio Gómez was sent off at Parken.
Liverpool meantime rediscovered their mojo on Wednesday, coming from a goal down to demolish Rangers 7-1 at Ibrox.
Mo Salah bagged the fastest hat-trick Champions League history, timed at six minutes and two seconds.
They need just a point from their final two games to get through.
Will this huge game be exactly what Liverpool need to reinvigorate their season, or will Manchester City be simply too strong at Anfield?
Liverpool team news
Defenders Joël Matip and Trent Alexander-Arnold went off injured at Arsenal last weekend, and both are out of this one too.
Andy Robertson came on for 22 minutes at Ibrox, so could start for the first time since 7 September.
This’ll be Virgil van Dijk’s 70th Premier League appearance for Liverpool at Anfield and, amazingly, he’s still never lost one; will this be the day?
Thiago will return in midfield, probably alongside both Fabinho and Jordan Henderson.
Mo Salah’s hat-trick off the bench at Ibrox will surely earn him start here, alongside Darwin Núñez and Roberto Firmino, both of whom scored at Arsenal and then against Rangers.
Luis Díaz has been ruled out until after the World Cup.
Manchester City team news
Pep Guardiola meanwhile rotated his squad in Denmark on Tuesday, but all the big-hitters will be back for this one.
There’s no more big-hitter than Erling Braut Håland right now; he’s already scored 20 goals this season, averaging one every 47.5 minutes in the Champions and Premier League.
They are without Kyle Walker and Kalvin Phillips, neither of whom are likely to be back in time for the World Cup.
Rúben Dias, Bernardo Silva and Phil Foden, who all came off the bench in midweek, will start here.
Kevin De Bruyne has nine Premier League assists to his name; the record for a single-season is 20.