Nigerian striker Osimhen, who played his first minutes since the international break in a goalless draw with Verona, is expected to lead the line for Napoli as they look to overturn a 1-0 deficit from the first leg and reach the last four for the first time in their history.
Napoli will be without midfielder Andre-Frank Zambo Anguissa and starting centre-back Kim Min-jae, both of whom are suspended due to their bookings in the first leg.
However, Spalletti believes that Osimhen's attacking threat will have a bigger impact on the game than the absences of these key players. Spalletti told reporters, "We earn more with the presence of Osimhen than we lose with those absences because he will probably be left one-on-one as Milan come after you, they like to press."
Osimhen has been in excellent form this season, netting 25 times in 30 matches in all competitions, including four goals in five Champions League appearances.
Spalletti and Juan Jesus, who will replace Kim in the Napoli defence, both emphasized the need to be crafty in such a big game and hinted at the importance of Osimhen's form in overcoming the deficit.
"Victor will be a problem for Milan's defense because he's on form, he's our top scorer, and he shows every match that he's got the desire to keep doing even more," said Juan Jesus. "Let's hope he keeps doing that."