The German judge at Cambodia's UN-backed genocide tribunal says he is resigning over government statements opposing any further prosecutions.
Siegfried Blunk said the statements could "be perceived as attempted interference by government officials".
He said he was resigning so that his independence and the court's integrity could not be doubted.
Mr Blunk has been under fire over his handling of two new cases. Human Rights Watch called for his resignation.
Up to two million Cambodians are thought to have died - from starvation, overwork or execution - during the four years of Khmer Rouge rule.
The genocide tribunal was established to bring the regime's leaders to justice. But so far only one case - against former Khmer Rouge prison chief Duch - has been successfully concluded.
Four top leaders including Pol Pot's deputy, Nuon Chea, are due to go on trial in the coming months.
'No hope'
It is the handling of the third and fourth cases - involving five people alleged to have been senior Khmer Rouge commanders - that has caused the current row.
Mr Blunk and his Cambodian counterpart You Bunleng sparked concern among rights groups in April after they closed their investigation into the third case.
The group said that the tribunal had been "subject to frequent politically motivated interference" from the ruling party, many of whom were former Khmer Rouge leaders.
Prime Minister Hun Sen - at one point a mid-ranking Khmer Rouge commander - as well as his information minister and foreign minister have all separately made it clear in recent months that they do not want further prosecutions after the second trial has concluded.
Mr Blunk's resignation statement came through the court.
It said that while he was not influenced by political statements, "his ability to withstand such pressure by government officials to perform his duties independently, could always be called in doubt, and this would also call in doubt the integrity of the whole proceedings" of the two new cases.
Judge Blunk has been a controversial figure since he took over from French judge Marcel Lemonde to investigate cases three and four, the BBC's Guy De Launey in Phnom Penh says.
Many of his own international staff have been so dismayed by the way the crimes were being investigated that they quit in protest. One called Mr Blunk's office "dysfunctional", our correspondent says. Read more!