The stand-up comedian and actor had been battling the disease before he passed away in hospital in NY, his manager confirmed.
Since the sad news was announced, tributes have flooded in for the late comedian - who was the older brother of actor Eddie Murphy - on social media.
"Charlie is actually my best impression, " he said.
Charlie's wife, Tisha Taylor Murphy, died in 2009 from cervical cancer.
Charlie Murphy penned the scripts for Norbit and Vampire in Brooklyn, as well as being one of the creative forces behind Chappelle's Show.
The New York City born comic and actor starred on Chappelle's Show, Are We There Yet?, and has lent his voice to the animated series The Boondocks. Thank you for the outpouring of condolences and prayers.
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After Chappelle left the program, Murphy and co-star Donnell Rawlings hosted episodes compiling the sketches shot before the host's departure and dubbed the "lost episodes". They had 2 children together, with one child from Charlie's previous relationship.
Charlie had been seeking treatment with chemotherapy and his family including his younger brother Eddie, was shocked by his death because it was believed he would be getting better. Most recently, Murphy appeared on the Comedy Get Down tour with Cedric the Entertainer, Eddie Griffin, D.L. Hughley, and George Lopez.
"I've been doing him since I was two or three".
"We just lose one of the funniest most real brothers of all time", tweeted out Chris Rock when he heard of his passing.
Charlie Murphy would become a household name in 2004 with his first appearence on Chapple's Show.
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