The Ecuador international moves to the Rossonero in a permanent transfer, signing a deal to 2030.
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Estupinan made 104 appearances for Albion, scoring five goals.
Brighton boss Fabian Hurzeler said, “I have enjoyed working with Pervis and he has made a significant contribution to the club during his time here.
“He is at the stage of his career when he wants a fresh challenge and this opportunity to play in Serie A gives him that.
"I’d like to thank Pervis for his contribution to the club and wish him all the best for the future.”
Brighton and Milan are yet to disclose the transfer fee involved.