Tropical Cyclone Pam intensified to a maximum category five storm off Vanuatu on Friday and was already causing flooding in the capital Port Vila, officials said.
The Vanuatu Disaster Management Office issued red alerts for four provinces in the poor Pacific nation of 270,000 people, advising residents to shelter in evacuation centres.
Aid agencies said many people living in flimsy slum accommodation were particularly at risk.
Meteorologists said Pam had hit category five intensity, with winds in the eye of the storm set to reach 230 kilometres an hour (143 mph).
The cyclone was expected to track 100 kilometres off the island nation's east coast.
But Vanuatu's meteorology service said residents should still brace for winds of 165 kilometres per hour (102 miles per hour) along with flash flooding, landslides and "very rough to phenomenal seas".
UNICEF spokeswoman Alice Clements said Port Vila resembled a "ghost town" as people battened down.
"Tonight is really the night we're going to find out," said the official with the UN children's agency.
"The winds have definitely increased, the palm trees are blowing around like crazy, you're starting to get that kind of howling wind coming through," she said.
Clements said there was little hope that the cyclone might make a late change of course and largely spare Vanuatu.
"They're super unpredictable but the centre of the storm is tracking really close by, so even if it's not a direct hit there's going to be really significant impacts," she said.
Save the Children’s Vanuatu director Tom Skirrow said up to 50,000 children were at risk in the nation, where two-thirds of the  population rely on subsistence agriculture.
“We have been going door to door in some of the poorest slum areas and I’m hugely concerned that not enough is being done to make sure children and families are safe as this huge storm approaches," he said.
"Thousands of families are living in makeshift, flimsy houses which will not withstand the immense winds and rain we’re expecting. Families need to urgently evacuate to safe buildings or the results could be catastrophic.”
Cyclones, known as hurricanes in the northern hemisphere, are a common occurrence in the South Pacific at this time of year.
Tropical Cyclone Lusi swept across Vanuatu in March last year, killing 11 people and damaging crops and infrastructure.