Matri says winning the Europa League would change the dynamic in the city.
He said on DAZN: "Victory in the Europa League could make the conquest of the Scudetto more bitter, more so than the derby victory.
"It's a single match that makes the season bitter."
Fellow pundit Valon Behrami, added: "A victory in Europe changes the vision of things a lot, we saw what happened with Jos Mourinho's Roma. A Milan in second place with a Europa League title in the trophy cabinet would make for an excellent season."