Castrillón is a Spanish surname. Notable people with the surname include:
Álvaro Mejía Castrillón (born 1967), Colombian road bicycle racer Eduardo Crespo y García-Castrillón, 8th Count of Castillo Fiel (fl. 1963–1989), Spanish aristocrat Darío Castrillón Hoyos (1929–2018), Colombian Cardinal of the Catholic Church Jaime Castrillón (born 1983), Colombian footballer Manuel Fernández Castrillón (–1836), major general in the Mexican army