Milan look to Ante Rebic, Rafael Leao and returning Fikayo Tomori for the Coppa Italia Round of 16, while Andriy Shevchenko gives Kelvin Yeboah his Genoa debut.
It kicks off at San Siro at 20.00 GMT, you can follow the build-up and action as it happens from this game and Napoli-Fiorentina on the LIVEBLOG.
The winners, decided after 90 minutes, extra time or penalties, will meet either Lazio or Udinese in the quarter-final next month.
Milan have Tomori and Rebic back from COVID-19 and injury respectively, joined by Daniel Maldini and Junior Messias, with Giroud leading the way.
Zlatan Ibrahimovic, Davide Calabria, Simon Kjaer, Alessio Romagnoli, Samu Castillejo, Pietro Pellegri, Franck Kessie, Fode Ballo-Toure and Ismael Bennacer are unavailable.
Andriy Shevchenko returns to San Siro as an opponent, although reports suggest it will be his final game on the Genoa bench regardless of the result.
He only took over from Davide Ballardini two months ago, but the dismal results including a home defeat to Spezia at the weekend sealed his fate.
There are again numerous absentees, including Nikola Maksimovic, Domenico Criscito, Andrea Cambiaso, Valon Behrami and Yayah Kallon.
He does give January signing Yeboah his debut after the weekend arrival from Sturm Graz for €6.5m, in a trident with Felipe Caicedo and Caleb Ekuban.
The nephew of Tony Yeboah scored 14 goals with eight assists in 28 competitive games for the Austrian club this season.
Milan: Maignan; Kalulu, Gabbia, Tomori, Theo Hernandez; Tonali, Krunic; Messias, Maldini, Leao; Rebic
Genoa: Semper; Hefti, Vanheusden, Ostigard, Vasquez; Portanova, Badelj, Melegoni; Yeboah, Caicedo, Ekuban