Di Stefano is a patronymic Italian surname meaning "(the son) of Stephen". Notable people with the surname include:
Alfredo Di Stéfano (1926–2014), Argentinian-Spanish footballer Andrea Di Stefano (born 1972), Italian actor Francesco di Stefano (c. 1422–1457), Italian painter Giordana Di Stefano (1995–2015), Italian femicide victim Giovanni di Stefano (disambiguation), several people Giuseppe Di Stefano (1921–2008), Italian tenor Manlio Di Stefano (born 1981), Italian politician Sergio Di Stefano (1939–2010), Italian voice actor Vincenzo di Stefano da Verona, Italian painter Phil DiStefano (born 1946), 11th Chancellor of University of Colorado Boulder