"Vincent Cassel confirms that he is separating from his wife Monica Bellucci by mutual agreement," said a statement released by Cassel's spokeswoman, without revealing further details.
In Italy, Bellucci's representatives also announced the separation to an Italian press agency, confirming a story published Saturday by the French edition of Closer magazine.
The pair met while filming French film "The Apartment" in 1996.
They married several years later and had two daughters: Deva, 8, and Leonie, 3.
Bellucci, from Italy, has appeared in several Hollywood films including "Matrix Reloaded" and Terry Gilliam's "The Brothers Grimm".
Cassel shot to fame with his role as a troubled young man from the Parisian suburbs in the critically acclaimed "La Haine".
He is also known for his roles in popular American films such as "Ocean's Twelve" and "Black Swan".