Milan opt for Rade Krunic in the trequartista role with Rafael Leao and Olivier Giroud, as they need a point against RB Salzburg to reach the Champions League Round of 16.
It kicks off at San Siro at 20.00 GMT.
The Rossoneri put themselves in pole position to follow Chelsea into the knockouts with a 4-0 win away to Dinamo Zagreb.
It means they only need a point to secure qualification, but RB Salzburg know they can leapfrog them with a win here.
Stefano Pioli rested numerous players for the 2-1 Serie A defeat to Torino, as the injury list remains extensive, missing Mike Maignan, Davide Calabria, Alexis Saelemaekers, Alessandro Florenzi, Zlatan Ibrahimovic and those not on the Champions League list, Aster Vranckx, Yacine Adli and Malick Thiaw.
Fikayo Tomori returns from suspension to bolster the defence.
While Brahim Diaz and Charles De Ketelaere have been battling for the trequartista role all season, it is Krunic who gets the nod this time.
RB Salzburg drew 1-1 with Milan in Austria and make this visit without injured Fernando and Nicolas Capaldo, while Junior Adamu and Omar Solet are carrying thigh issues, but start regardless.
Noah Okafor is their Champions League top scorer with three goals in five games.
They’ll be well supported at San Siro, as circa 4,000 fans have made the journey from Salzburg.
Milan: Tatarusanu; Kalulu, Kjaer, Tomori, Theo Hernandez; Bennacer, Tonali; Rebic, Krunic, Leao; Giroud
RB Salzburg: Kohn; Dedic, Wober, Pavlovic, Solet; Kjaergaard, Gourna-Douath, Seiwald; Sucic; Adamu, Okafor
Ref: Lahoz (ESP)