Abel Hernandez could be out for at least six months after the Palermo man damaged cruciate knee ligaments.
The striker picked up the injury in a training ground clash while he was on international duty with Uruguay this week.
Despite hopes that he had only badly twisted his right knee, scans have now confirmed more serious damage.
The South American, still just 22-years-old, will fly back to Italy on Friday before going under the knife.
Hernandez had played in all seven of the club’s League games so far this term, but he had yet to score for the Rosanero.
See the latest Serie A predictions and betting tips with Eurotips.co.uk