Lavezzi, who was on target in his team's 3-1 win at Cesena in their opener, is doubtful for this weekend's clash after sustaining a muscular problem in midweek.
"We hope that Lavezzi will recover," team-mate Edinson Cavani said. "But if he doesn't, I'm sure whoever replaces him will be up to the task."
The two sides go into the encounter at a sold-out Stadio San Paolo on the back of morale-boosting European results.
Walter Mazzarri's side drew 1-1 at Manchester City in their first Champions League group game, while Milan held Barcelona to a 2-2 tie at the Nou Camp.
Those results, however, came at a price for both sides.
Milan lost midfielders Massimo Ambrosini and Kevin-Prince Boateng to injury while Lavezzi got hurt for Napoli..
Should Lavezzi fail to recover, Mazzarri will field Goran Pandev and Marek Hamsik in support of Cavani.
Cavani, who scored against City, cannot wait for the chance to get one over on Milan.
"It's an important game," he said. "We want to avenge our two defeats against them last season.
"In order to beat them, we will have to play with the mentality that Mazzarri has transmitted to us.
"We have a good team and we hope that Lavezzi can play.
"They are missing some champions but they are strong."
Milan, who were held to a 2-2 home draw by Lazio in their Serie A opener, are also without defender Philippe Mexes and injured strikers Zlatan Ibrahimovic and Filippo Inzaghi. Antonio Cassano will partner Alexandre Pato in attack.