Roberto Martinez's side are unbeaten at Goodison Park this season and can go level on points with the Reds, who have not lost against their neighbours in five league clashes
Roberto Martinez's men have racked up three wins and two draws on their own turf in the Premier League this season, and three points at the weekend would see them move level with their local rivals.
Everton head into the fixture looking to extend a four-match unbeaten run in the top flight, although their last two games have both produced 0-0 draws.
Successes over Hull and Aston Villa were followed by stalemates against Tottenham and Crystal Palace, and Martinez will hope for a better performance in front of goal as they aim to improve their league position of sixth.
The Spaniard takes charge of his maiden Merseyside derby after joining the club in the close-season, and the 40-year-old believes the fact the two sides are so closely matched in the table heightens the game's importance.
"I am delighted to be getting ready for a first Merseyside derby and really looking forward to it," he said. "When you add all the connotations of a derby with the importance of the points, I think this fixture is going to be as big and good as a football game can be."
Everton are boosted by the return of full-back Tony Hibbert, who is available following a calf injury, while close-season signing Antolin Alcarez (groin) looks set to finally put his injury woes behind him and is contention to make his first Everton appearance.
Martinez admitted the duo are unlikely to start against Liverpool as they step up their match fitness, while Arouna Kone and Darron Gibson (both knee) remain long-term absentees.
Liverpool - who have not lost to Everton in their last five Premier League encounters - head into the clash buoyed by 4-0 rout of Fulham before the international break.
A Fernando Amorebieta own goal and a strike from Martin Skrtel established a two-goal cushion, before Luis Suarez's double completed the comfortable victory.
That result left the Anfield outfit in second place, just two points adrift of table-toppers Arsenal.
Liverpool's last defeat to Everton came in a 2-0 reverse at Goodison Park in October 2010, with strikes from Tim Cahill and Mikel Arteta settling the game on that occasion.
Brendan Rodgers' men lead the head-to-head record between the sides with 88 wins to 66, although last season's fixtures both produced draws.
Full-back Jose Enrique will be absent for the visitors. The Spaniard is set for an extended lay-off as he is likely to require an operation on a knee injury, while Iago Aspas (thigh) and Sebastian Coates (knee) also remain sidelined.
Daniel Sturridge has been struggling with a dead leg, but Rodgers is optimistic the striker - who has scored eight Premier League goals this term - will be fit to feature.