Known as “the butcher” for his brutality, Ta Mok – whose real name was Ung Choeun – briefly led the Khmer Rouge during its final days.
He was one of two former senior officials of the movement in detention awaiting trial for crimes against humanity.
Ta Mok had been in custody since his capture in 1999 and was being treated in a military hospital for high blood pressure, tuberculosis and respiratory complications. He had been in and out of a coma since last week.
He was believed to be about 82.
Reign of terror
The communist group’s extremist policies during its rule in the late 1970s led to the deaths of an estimated 1.7 million people through starvation, overwork, disease and execution.
Youk Chhang, the director of the Cambodian documentation centre, an independent group researching the Khmer Rouge’s crimes, said: “It’s sad news … it’s outrageous.
“Some people may be happy with this but not the victims who have been waiting for justice for a long time.”
Judges and prosecutors were sworn in this month for the start of UN-backed trials of former Khmer Rouge leaders on charges of genocide and crimes against humanity.
The other detained former leader is Kaing Khek Iev, also known as Duch, who headed the notorious S-21 torture centre in Phnom Penh.