Born on the 11th January 1930 he studied composition at the San Pietro a Maiella in Naples, under the guidance of Achille Longo, who was also his uncle. De Masi got interested in film music when Longo was asked to compose a soundtrack for a film, and he asked De Masi to be his assistant. De Masi's filmography includes scores for over 200 films and TV series, ranging from spaghetti westerns and sword and sandal epics to gialli and horror films, such as Lucio Fulci's "Lo squartatore di New York" (The New York Ripper).
De Masi also scored several action films, such as Enzo G. Castellari's "Quel maledetto treno blindato" (Inglorious Bastards), but he is best remembered for his work on spaghetti westerns. Unlike most other composers, De Masi started writing western scores slightly earlier than the genre's most influential musician, Ennio Morricone. As De Masi's music was less influenced by Morricone, his style had a distinctive sound. Many of his songs were performed by the low-voiced member of the I Cantori Moderni choir, Ettore "Raoul" Lovecchio.
De Masi was also very interested in classical music. He taught at the Santa Cecilia Conservatory, also conducting the conservatory's orchestra. In an interview, De Masi listed Giovanni Pierluigi da Palestrina, Karlheinz Stockhausen, Maurice Ravel and Dmitri Shostakovich as his main classical influences.
He died of cancer at the age of 75 on the 6th November 2005.