The Italians are currently third in Group F, level on six points with Arsenal and Borussia Dortmund, who have a better goal average that Napoli and who face each other in Germany on Wednesday in the other pool game.
"This is a really difficult group in which you risk not progressing even with 12 points," Benitez told a press conference. "The only thing that matters is that we win.
"After that we can start making calculations regarding goal differential and the rest.
"Our aim is to progress to the next round of the competition although a win would assure us of a place in the Europa League."
Marseille lie at the foot of the standings with no points to their name but Benitez has warned his side not to take the French outfit lightly.
"They have good players," he said. "They are lacking a bit of confidence but they are a strong side.
"They will come here determined to prove their quality.
"Everyone expects us to win but we have to go out and earn it."
Napoli are currently second in Serie A, three points adrift of league leaders Roma.
Benitez's side goes into the encounter at the San Paolo stadium riding a four-match winning streak in all competitions.
In-form Jose Maria Callejon is set to partner Marek Hamsik up front, with the Spanish player having been on target in three of his team's last four games, including Saturday's 2-1 triumph over Catania.
Marseille were held to a 1-1 draw at Stade Rennes on Saturday to see their winless run extended to six games.
Their poor run of form - which saw three straight league defeats in October and two losses in the Champions League - has dropped Elie Baup's outfit to fifth place in Ligue 1, 10 points adrift of pacesetters PSG.
"We are going through a delicate time," Marseille defender Souleymane Diaware said to www.om.net. "The point taken at Rennes did us good from a mental standpoint and it has given us some calmness to focus on our next game.
"I'm not worried because I believe it will not be long before we start showing our true colours."
OM welcome back forward Andre Ayew from suspension.
The hosts will be without midfielder Giandomenico Mesto, who underwent ACL reconstruction in his right knee on Monday and will be sidelined for four months.