Hernandez, who has netted only once this season having scored 22 in Hull's promotion campaign last term, was injured nine minutes into the 2-1 victory over Southampton at the weekend.
"He has been withdrawn from international duty," the Premier League club said in a statement.
Uruguay, who meet Ecuador on Thursday and Chile next Tuesday, are second in World Cup South American qualifying, one point behind leaders Brazil after 10 matches.
(Reporting by Martyn Herman; Editing by Tony Jimenez)
