A win in France would give Arsene Wenger's side 12 points in Group F, but qualification with one match remaining would still not be sealed unless Borussia Dortmund fails to beat Napoli.
Key to Arsenal's form has been the efforts of Aaron Ramsey and Olivier Giroud, with the former having netted 11 goals in all competitions so far this season.
Ramsey's contribution from midfield has been crucial for a side which is still short on firepower beyond Giroud.
The 27-year-old Frenchman netted both goals in the 2-0 Premier League win over Southampton on Saturday, taking his tally to 10 for the season, but the club's fans will be hoping for a new signing in January to give him some support.
Theo Walcott returned from an abdominal injury in the win against Southampton and is a welcome inclusion for a side still missing Lukas Podolski (hamstring), Alex Oxlade-Chamberlain and midfielder Abou Diaby (both knee).
Arsenal won the first meeting between these two sides in France in September, with goals from Walcott and Ramsey giving them a 2-1 success.
They also met twice in the 2011-12 Champions League, and although the fixture in London ended goalless, Ramsey scored a late winner in a 1-0 victory for Arsenal in France.
While Arsenal tops the group with nine points, Marseille is rock-bottom and is yet to get off the mark after losing all four of its matches so far.
Qualification is now beyond them, but coach Elie Baup will be looking for his side to restore some pride.
A winless run of seven matches put serious pressure on Baup, but successive Ligue 1 triumphs over Sochaux and Ajaccio have lifted Marseille to fourth in the table.
Youngster Florian Thauvin scored in Friday's 3-1 win at Ajaccio, his seventh goal in six matches for club and country.
Thauvin also netted a hat trick and provided two assists for France's Under-21s in a 6-0 romp against Armenia earlier this month.
Marseille has won just once in its 11 Champions League visits to England, losing six, and it will be without forward Andre Ayew, who could miss the next two months with a knee injury, while Rod Fanni (muscle strain) is also sidelined.
Lucas Mendes could return from an ankle injury though, after he was an unused substitute at Ajaccio.