Ruffo is a surname. Notable people with the surname include:

• Fabrizio Ruffo (1744–1827), Italian cardinal
• Fulco Ruffo di Calabria (1884–1946), Italian World War I flying ace
• Giordano Ruffo (1200-1256), Italian nobleman and early writer on equestrian medicine
• Paola Ruffo di Calabria (born 1937), queen consort of Belgium
• Tommaso Ruffo (1663–1753), Italian cardinal
• Polissena Ruffo (1400–1420), princess of Calabria

• Albert J. Ruffo (1908–2003), American politician
• Andrée Ruffo, Canadian judge
• Antonio Ruffo (1610s–1678), Sicilian politician, nobleman, patron, and collector
• Armand Garnet Ruffo (born 1955), Canadian scholar, filmmaker, writer and poet
• Bruno Ruffo (1920–2007), Italian motorcycle road racer
• Dennis Ruffo, Canadian music promoter
• Ernesto Ruffo Appel (born 1952), American-born governor of Baja California
• John Ruffo (born 1954), American business executive
• Johnny Ruffo (1988–2023), Australian singer, songwriter, dancer, actor and television presenter
• Leonora Ruffo (1935–2007), Italian film actress
• Marco Ruffo, Italian architect
• Pietro Ruffo (born 1978), Italian artist
• Titta Ruffo (1877–1953), Italian baritone
• Victoria Ruffo (born 1962), Mexican actress
• Vincenzo Ruffo (c. 1508–1587), Italian composer of the Renaissance

• Rufo (surname)