The 25-year-old joined Sevilla in 2007 but has not been a first-team regular in recent seasons, making just 19 appearances last term before being loaned out to Argentinian giants Boca Juniors.
However, he failed to make an impact during what was his first spell in Argentina’s top flight and Genoa have now moved for the forward by confirming the deal in a brief statement on the club's official website.
"Genoa communicates it has reached an agreement with Sevilla for the acquisition of the sporting rights of forward Diego Perotti," it read.
"The player has signed a four-year contract."
Argentina international Perotti has two caps for his country but has not represented the Albiceleste since 2011.
He scored four goals in eight appearances in Sevilla's Europa League-winning campaign last season.