In the club's last Champions League home game, Wenger chose to leave Van Persie on the bench to rest him for the club's north London derby at Tottenham the following weekend.
But with the Dutchman's confidence sky high after firing in seven goals in his last four matches, Wenger is unlikely to do the same against Marseille.
"It's hard to take a player out when he is playing so well," Wenger said. "It's very hard to explain to the rest of the team that you are not going to play Van Persie when he has scored so many recently.
"When a player is playing so much confident football it's difficult to take him out. "He is kind of always a victim of his success."