Favino was born in Rome, Italy. Since the early 1990s, he has appeared in more than forty European films and television series, including Gabriele Muccino's "The Last Kiss," Gianni Amelio's "The Keys to the House," Giuseppe Tornatore's "The Unknown Woman," and Ferzan Ozpetek's "Saturn in Opposition." In 1999 he starred in the HBO film "Excellent Cadavers," an adaptation of Alexander Stille's novel of the same name.

In 2006 he received the David di Donatello Award — the Italian equivalent of the Oscar — for his role in the crime film "Romanzo Criminale," directed by Michele Placido.