Dr Abdul Momen, the Bangladesh Ambassador to the UN, told bdnews24.com that he had passed away at 11:30pm Thursday Bangladesh time at Bellevue Hospital.
"The doctors have announced him dead moments before," Momen told bdnews24.com at 11:32pm.
Wife Meher Afroz Shaon, younger brother Mohammad Zafar Iqbal and publisher Mazharul Islam were at the Bellevue Hospital at the time of death.
President Zillur Rahman, Prime Minister Sheikh Hasina and Opposition Leader Khaleda Zia have been leading the nation in mourning the novelist, playwright and filmmaker.
Tens of thousands of tributes began to pour in on social networking sites. One Facebook posting predicted: "The tsunami of emotion will hit Bangladesh during his funeral."
Arriving in New York on Sept 14 last year for treatment, he had two major surgeries on his colon since June 12 at Bellevue. He had earlier gone through 12 chemotherapy cycles at the Memorial Sloan-Kettering Cancer Centre.
The writer's condition was stated critical after he had undergone the second surgery on June 21, when doctors detected infection of an unknown virus on his body and were unable to treat it. When news of his critical health first came out, legions of his fans expressed concern.
Humayun was diagnosed with colon cancer during a routine check-up in Singapore last year.
On May 11, the writer had come back home after taking treatment for eight straight months in New York before going for the surgeries. He had spent 20 days at Nuhash Palli, his retreat at Gazipur which the writer had said he missed the most while living abroad.
Born in Mymensingh in 1948, he studied chemistry at the Dhaka University and later taught chemistry in his alma mater.
He left teaching when he became a fulltime writer and filmmaker.
Humayun Ahmed had a meteoric rise in Bangla literature. He penned his first novel, Nondito Noroke while still a student at the DU, gaining immediate popularity and critical acclaim. Equally successful was his second novel, Shankhanil Karagar (The Conch-blue Prison).
Humayun went on to become one of the most prolific writers in Bengali literature, with around 150 novels to his credit. He also wrote science fiction; he was a charismatic creator of such characters as Himu and Misir Ali.
His first television drama was Ei Shob Din Ratri (Tale of our daily lives), followed by Bohubrihi, Ayomoy "The man who would not die", Kothao Keu Nei (Nobody Anywhere). The last drama had such an influence on the people that they took out protest processions after the protagonist of the drama, Baker Bhai, was wrongly convicted and executed. Public prayers and death anniversaries were observed for this fictional character by his fans. His another popular television piece was Nakshatrer Raat (The Night of the Stars), exploring many facets of modern human life and its relationship.
Bohubrihi was one of the most successful productions of Bangladesh Television.
His making was so unique in its manifestation of characters that anybody in the country could tell the maker was none but Humayun by seeing any given sequence or dialogue.
Humayun won the National Film Award in total eight categories, including Best Picture and Best Director, on his debut film, "Aguner Parashmoni", based on the liberation war.
Liberation War and middle-class life crisis often were the themes he liked to work on often. The execution of his father by the Pakistani occupation force had a great impact on his works.
Ahmed also wrote few songs for his own films and plays. Some of the notables are titled as Ami Aaj Bhejabo Chokh Somudrer Joley, Chadni Poshor Ratey and Amaaar Achey Jol.
Winner of Bangla Academy Award in 1981, Ekushey Padak in 1994 and three National Film Awards (Best Story in 1993, Best Film 1994 and Best Script in 1994), Humayun continued writing even when he was being treated in New York.
On Jan 13, the government gave the writer a diplomatic position – Senior Special Adviser -- at the country's Permanent Mission at the United Nations, allowing him certain privileges in the city where he was being treated and living with the family.
The writer is survived by two sons—Ninit and Nishad— with second wife Shaon, and three daughters— Nova, Shila, Bipasha—and son Nuhash with his previous wife Gultekin.
Ever since diagnosed with the cancer, the writer had announced should he win the battle against cancer, he would build a cancer hospital in Bangladesh.