Klopp's side have now won an astonishing 17 successive matches at Anfield and their unbeaten run in the Champions League at home extends back to October 2014.
However, their only defeat in normal time this season did come against the Italians in the reverse fixture.
Carlo Ancelotti's side can also seal their qualification with a win but have been hampered by injuries as unrest behind the scenes between key players and the club's owner continues to dominate headlines during a disappointing start to the Serie A season.
Here is everything you need to know about the game:
Liverpool: Mohamed Salah is in line to return after recovering from an ankle injury. Fitness concerns over Andrew Robertson have also been eased after the full back completed 90 minutes against Crystal Palace without issue.
Salah’s return could cause a positional switch for Alex Oxlade-Chamberlain while Fabinho is a certainty to start having been ruled out of Saturday’s Premier League fixture against Brighton due to suspension.
Joel Matip’s injury will keep him out of the game, however, Xherdan Shaqiri could return from a nagging calf problem.
Napoli: Ancelotti’s side are missing two of their key forwards, Arkadiusz Milik and Lorenzo Insigne, due to stomach and elbow issues respectively.
Their absence means Fernando Llorente could start alongside Dries Mertens, after both sides scored in the reverse fixture in Naples.
Man City XI: Alisson; Alexander-Arnold, Lovren, Van Dijk, Robertson; Henderson, Fabinho, Oxlade-Chamberlain; Salah, Firmino, Mane
Chelsea XI: Meret; Di Lorenzo, Manolas, Koulibaly, Hysaj; Callejon, Allan, Elmas, Fabian Ruiz; Lozano, Mertens
When is it?
The match is on Wednesday 27 November.
When does it kick-off?
The match gets underway at 8:00pm.
How can I watch the match?
The match will be available to watch and stream on BT Sport 2 and the BT Sport App.
What are the odds?
Liverpool to win: 2/5
Napoli to win: 13/2
Liverpool have been relentless this season and, despite being forced into a pattern of grinding out late wins, the possibility of ensuring their qualification – and securing a much-needed rest for some of their senior players in their final game against Salzburg – coupled by the fiery fortress atmosphere at Anfield will haul Klopp’s side through a tricky encounter.
Liverpool 3-1 Napoli