The aid operation in north-eastern Syria is being "overwhelmed" as the number of people displaced by the government offensive in Idlib rises, the UN said on Monday.
Since early December 900,000 people have been forced to flee, most of them women and children, it said.
The UN added that health facilities and schools were being targeted.
The warning came as President Bashar al-Assad vowed to continue army operations in northern Syria.
"The battle for the liberation of the provinces of Aleppo and Idlib continues," he said, after his forces made new advances over the weekend.
In a statement on Monday, the UN's Under-Secretary-General for Humanitarian Affairs, Mark Lowcock, warned that "the biggest humanitarian horror story of the 21st Century" could only be avoided with a ceasefire.
Babies and small children were dying because of the cold, he said, with people forced to sleep outside in freezing temperatures as camps were full.
Mr Lowcock said violence in the region was indiscriminate and that basic infrastructure was being targeted.
"We are now receiving reports that settlements for displaced people are being hit, resulting in deaths, injuries and further displacement," he added.
He said a major relief operation being managed from across the border in Turkey was being overwhelmed.
Before the conflict began in 2011, Idlib was home to about 1.5 million people. However, this number has since doubled as the Syrian government retook former opposition areas elsewhere in the country.
The province is the final major rebel-held stronghold in Syria, but the advance of the Syrian government forces, backed by Russian forces and Iranian-backed militias, has put further pressure on the displaced population.
Turkey, which supports many of the rebel groups in the province, has also closed its border with Syria.