Dupont has undergone surgery on a broken cheekbone suffered in France's last Pool A match against Namibia two weeks ago.
While the inspirational half-back is expected to return to the team during the tournament, he has yet to be given the green light.
Lucu got the nod over Baptiste Couilloud, who starts on the bench against the Azzurri, as he did for the 96-0 thrashing of Namibia.
"Maxime has never let us down, he has always performed for the France team showing his qualities: he is totally selfless," said Galthie.
"He gives a lot to the team, both in attack and in defence. He also has a good kicking game, he's very brave.”
Lucu will team-up with his half-back partner at Bordeaux-Begles, Matthieu Jalibert, for the match against France's trans-Alpine rivals.
"He's a ninth forward and he compliments Matthieu Jalibert," said Galthie.
"He (Jalibert) shows up, he performs. They play together on a daily basis in their club, that brings them closer together.
"That allows them to develop a form of proximity, reflexes aimed at making their game and their combinations more fluid.”
'It's going to be brutal’
The only other change to the starting lineup for Friday's match in Lyon sees Gregory Alldritt returning at No.8, with Anthony Jelonch moving to blindside and Francois Cros dropping to the bench.
Charles Ollivon captains the side from openside in the absence of Dupont after having been Galthie's skipper since the former scrum-half became head coach four years ago.
Dupont had taken over the reins from Ollivon for the 2022 Six Nations after the Toulon back-rower suffered a serious knee injury.
"Charles was captain when I took over, he was a great captain," said Galthie.
"He was injured, he worked very hard, he has come back a long way on his own and he comes back to the captaincy.
"Some people could have forgotten who Charles is, now is the time to pay tribute to him.”
France must avoid defeat against the Azzurri to book their quarter-final spot, while a victory will guarantee them first place in the pool.
They have not lost to Italy since 2013 and only three times in 47 Tests.
And although Italy come into the match on the back of being crushed 96-17 by New Zealand, Ollivon is expecting them to perform more like they did in a narrow Six Nations defeat to France in February.
"We don't doubt that they won't show the same face they did against New Zealand," said the captain.
"They will be desperate to show more commitment, they won't miss so many tackles, that's obvious.
"It will be a totally different match, we'll have to take it seriously for 80 minutes.
"There will be a huge level of commitment, it's going to be brutal."
France team (15-1): Thomas Ramos; Damian Penaud, Gael Fickou, Jonathan Danty, Louis Bielle-Biarrey; Matthieu Jalibert, Maxime Lucu; Gregory Alldritt, Charles Ollivon (capt), Anthony Jelonch; Thibaud Flament, Cameron Woki; Uini Atonio, Peato Mauvaka, Cyril Baille
Replacements: Pierre Bourgarit, Reda Wardi, Dorian Aldegheri, Romain Taofifenua, Francois Cros, Baptiste Couilloud, Yoram Moefana, Melvyn Jaminet
Coach: Fabien Galthie (FRA)