The London club have sacked their young Portuguese manager since last month's first leg and face the Italians under interim boss Roberto Di Matteo, whose first taste of European action could be his last unless his players stage a stunning comeback.
If Chelsea needed any encouragement that their bid to book a quarter-final berth was not an impossible task, they only have look to fellow Premier League side Arsenal who fell just short when faced with a much bigger challenge last week.
Arsenal trailed 4-0 from their first leg at AC Milan but scored three goals at home to lose 4-3 on aggregate. Chelsea's job is easier than that even if Napoli are on a run of six successive wins in all competitions.
"From the first minute we have to try to create chances to score. We know they have very good strikers and we have to be careful with them, but we will press from the first minute," winger Juan Mata said on the club's website.
Mata's goal in Napoli could prove valuable as a 2-0 win in London would put England's only remaining representatives through on away goals.
"In football nothing is impossible and at Stamford Bridge we have had good results in the Champions League, so I think we can do it," the Spaniard added. "All the supporters will be cheering us, it's a final for us, and we can do it."
IMPORTANT ADVANTAGE
The return of captain John Terry to the starting line-up for Saturday's 1-0 Premier League win over Stoke City should provides a boost to their central defence for the return leg.
However, for all the hope Chelsea might have after back-to-back wins and clean sheets since Di Matteo took charge, they come up against a team on an even better run.
The only one of five debutants still in the competition, Napoli warmed up for their trip to London with a 6-3 victory over Cagliari in Serie A with all the goals coming from different players.
While they have never won in England, they did manage a 1-1 draw at Manchester City in the group stage this season which should give them confidence even if they are wary of Chelsea charging out of the blocks like Arsenal did against Milan.
"We have an important advantage but we should play as if it were 0-0," defender Paolo Cannavaro said.
"We are certainly going to have to suffer but with a little bit of concentration in the first few minutes, we can do it.
"The first half will be very important, you just have to look at AC Milan who were trailing by 3-0 at halftime."
Napoli coach Walter Mazzarri will be serving the second of a two-match touchline ban during Wednesday's game.
Probable teams:
Chelsea: 1-Petr Cech; 2-Branislav Ivanovic, 24-Gary Cahill, 26-John Terry, 3-Ashley Cole; 8-Frank Lampard, 7-Ramires; 23-Daniel Sturridge, 10-Juan Mata, 5-Michael Essien; 11-Didier Drogba
Napoli: 1-Morgan De Sanctis; 14-Hugo Campagnaro, 28-Paolo
