Rafa Benitez's side have won two of their three Champions League Group F encounters but sit third, behind leaders Arsenal and Borussia Dortmund on goal difference.
In a match that could prove crucial in their hopes of reaching the round of 16, the Partenopei are heavy favourites to beat the struggling Phoceens.
The French side have lost all three of their Champions League fixtures and have slid to fifth in Ligue 1 after a dreadful run of form that has seen them fail to win any of their last six matches in all competitions.
Napoli have not lost any of their five previous home games in the Champions League, winning four, and defeated Marseille 2-1 in France last month thanks to goals from Jose Callejon and Duvan Zapata.
Callejon has now scored eight goals in 12 appearances in Europe's premier club competition, with seven of them coming for former club Real Madrid.
Napoli have not lost a Serie A match at home in 2013, winning 14 of 16 encounters, and they defeated Catania 2-1 on Saturday.
Miguel Angel Britos (collarbone) and Camilo Zuniga (knee) are on the sidelines for Benitez's men.
Marseille ended a five-match losing streak at Rennes on Saturday but needed goalkeeper Steve Mandanda to save a late penalty to earn a 1-1 draw.
Jordan Ayew scored his first league goal since January in that clash, but the pressure on coach Elie Baup has not eased, with Marseille having won just twice since the start of September.
They have kept just two clean sheets in the last two months and will need a miracle if they are to become just the second team ever to qualify from the group stages after losing their first three matches.
The feat was achieved by Newcastle United in the 2002-03 season but, in a group that also contains Arsenal and Borussia Dortmund, a repeat is unlikely.
Marseille will be without Lucas Mendes (ankle), while defender Rod Fanni (adductor) is unlikely to feature.