The Fiorentina striker spent four months out injured with a knee injury, but his return to fitness at the end of the season has seen him named in his country's provisional squad for the World Cup.
There has been much speculation as to whether Rossi will make the final 23-man squad that will travel to Brazil, but Prandelli is confident that his striker can impress at Craven Cottage.
"From what I've seen so far, I expect a big game from Rossi," Prandelli told reporters. "He has passed all the fitness tests and we've had positive signs from him in training.
"However, we have to consider how he will react from a psychological standpoint to contact.
"Rossi has been working to prepare in the best possible way for this game. In a way, for him the game against Ireland is as though it was his first World Cup game."
Prandelli announced in his pre-match press conference that Matteo Darmian will make his debut for the national side, while Marco Verratti, Gabriel Paletta and Ciro Immobile will all be in the starting lineup.