She was 78.
The actress was recently diagnosed with an unspecified form of cancer, reported Variety.
Lisi is survived by a son, Corrado, and three grandchildren, Franco, Federico, and Riccardo.
Born in Ancona 1936 as Virna Pieralisi, she began her film career as a teenager in 1953.
Her prominent roles in Italian post-war films include 1957 drama 'La Donna Del Giorno', 1963 crime movie 'Il Delitto' Dupre, with Alain Delon, and Mario Monicelli's 1965 Italo comedy classic 'Casanova 70', in which she co-starred with Marcello Mastroianni.
Tired of being relegated to playing 'seductive woman' in films, Lisi sought new types of roles and reportedly turned down the lead role in Roger Vadim's 'Barbarella' (1968), which went to actress Jane Fonda.
Her performance as the witchy queen Caterina de' Medici in 'La Reine Margot' (1994) won her the Prix Du Jury prize at the Cannes Film Festival and also a Cesar, which is the national film award of France.
She was honoured with a career Golden Globe in 2004.
Lisi's last film performance, after a 12-year hiatus, was in Cristina Comencini's upcoming comedy 'Latin Lover'.
