Ruffini is an Italian surname. Notable people with the surname include:
Angelo Ruffini, (1864–1929), Italian histologist and embryologist
Ernesto Ruffini (1888–1967), Archbishop of Palermo
Frederick Ernst Ruffini (1851-1885), American architect
Giovanni Ruffini (1807–1881), Italian poet and librettist
Oscar Ruffini (1858-1957), American architect
Paolo Ruffini (1765–1822), Italian mathematician and philosopher
Giuseppe or Joseph Ruffini (1690 - 1749), Tyrolese painter,