The 22-year-old came on in the second half after recovering from a head trauma in a Serie A match with Atalanta last month.
He missed Napoli’s last three matches in all competitions.
Osimhen came on in the 53rd minute before scoring his first goal in four months after the hour-mark.
Lorenzo Insigne scored the two other goals to help Napoli to a 3-1 win over Bologna.
The Super Eagles striker has now scored three goals for Napoli in the Serie A this season following a big-money move from Lille in the summer.