The Azzurri are seven points clear at the top of Group C, and have already guaranteed automatic qualification for next year's showpiece event in Poland and Ukraine.
Parma forward Sebastian Giovinco, who is Serie A's top scorer so far this season with five goals, will start alongside Antonio Cassano in Italy's attack.
"I would like to evaluate some players that have had limited playing time so far," Prandelli said in Monday's press conference. "Giovinco has a lot of quality and will start tomorrow [Tuesday]."
Prandelli's side held Serbia to a 1-1 draw on Friday to remain unbeaten in qualifying.
Giovinco will not be the only change to the side that started in Belgrade, with Palermo's Federico Balzaretti and Fiorentina's Mattia Cassani set to return to the team.
Moreover, Alberto Aquilani will replace Claudio Marchisio in midfield.
Despite those changes, Prandelli expects a strong finish from his players.
"I expect a further improvement on Tuesday with respect to our game in Serbia," Prandelli said. "The game against Serbia was an important test for us and I thought my team played well and showed a lot of character.
"I want the same focus and determination against Northern Ireland.
"I want my team to play well and to win."
Tuesday's game at the Adriatico Stadium will be Nigel Worthington's last as Northern Ireland manager.
The tactician announced on Monday he will be stepping down from his post after four years in charge.
"I feel the time has come (to step down) after four and a half years which have been fantastic for me as an individual," he said. "Sometimes when you try to get blood out of a stone there's only so much you can get.
"I think I've gone as far as I can with the group we've got.
"I feel it is only right to give the association and players the opportunity and time to move forward and that is why I have decided that Tuesday night's game will be my last in charge."
Northern Ireland have endured a disappointing qualifying campaign and last week's 2-1 home defeat to Estonia, their third straight loss, ended any hopes of claiming a play-off berth.
"There were genuine mistakes in the last three games - something that was not there in the previous matches," he said.
Worthington expects a difficult test for his players against Italy.
The Azzurri have conceded just two goals in qualifying and have found the back of the net 17 times in nine games.
"They are among the strongest teams in the world," he said. "Prandelli has done a good job to renovate the team."
To complicate matters for Northern Ireland, they are without injured Chris Brunt and Sammy Clingan while Jonny Evans and captain Aaron Hughes are doubtful for Tuesday's game.