"This would unleash a humanitarian nightmare unlike any seen in the blood-soaked Syrian conflict," he told reporters.
An estimated 3 million people live in Idlib - the major stronghold of active opposition to Assad militia. The UN has described it as a "dumping ground" for people evacuated and displaced from elsewhere in Syria during the seven-year war.
Assad has vowed to retake the region, backed by his Russian and Iranian allies. The Assad and Russian warplanes began air strikes in Idlib last week in a possible prelude to a full-scale offensive. They say they are targeting "terrorist groups".
"I understand that the present situation in Idlib is not sustainable and the presence of terrorist groups cannot be tolerated. But fighting terrorism does not absolve warring parties of their core obligations under international law," said Guterres.
Senior officials from Russia, Iran and Turkey met with UN Syria envoy Staffan de Mistura in Geneva on Tuesday. The presidents of Turkey, Iran and Russia met in Tehran on Friday (September 7) but failed to agree on a ceasefire in Idlib.
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