Santo Trafficante was the name of two powerful Tampa, Florida Mafia bosses, father and son:
- Santo Trafficante, Sr. (1886–1954) Sicilian-born mobster, and father of the powerful mobster Santo Trafficante, Jr.
- Santo Trafficante, Jr. (1914–1987) Powerful Tampa, Florida-born mobster, son of mobster Santo Trafficante, Jr.