Jurgen Klopp's men are flying in the Premier League but will be conscious of the fact that they have not gone past the fourth round of this competition since 2015.
Everton, bolstered by the arrival of Carlo Ancelotti, head into the game knowing that the club have not won at Anfield since the 1999-2000 season.
Here, Sports Mole looks at how Liverpool could line up for this fixture.
Out: Dejan Lovren (thigh), Fabinho (ankle), Joel Matip (knee), Xherdan Shaqiri (thigh), Alex Oxlade-Chamberlain (ankle), Naby Keita (groin), Rhian Brewster (ankle), Nathaniel Clyne (knee)
Following a remarkably hectic Christmas period, Klopp inevitably finds himself inundated with a number of injuries, and as such will want to rest players as much as possible.
Over on the right hand side of defence, for example, the German is likely to include youngster Ki-Jana Hoever, who has impressed in that position over the past year.
Over on the right, this is a perfect game for Harvey Elliott, Liverpool's only notable signing of last summer, to endear himself to the Anfield crowd having shown glimpses of talent in four appearances so far this term.
Having scored an injury-time winner at Anfield against the Toffees last season, the Belgian netted twice during the 5-2 success in the same fixture this time last month, and he will be expected to wreak further havoc against Liverpool's Merseyside rivals.