The huge explosion has led to emergency services desperately trying to locate survivors amid fears many people are trapped under the rubble of the four-storey building.
Video footage from the scene of the Antwerp explosion shows the building reduced to a pile of debris.
Firefighters can be seen attempting to access the building as they attempt to locate any trapped survivors.
The four-storey building is thought to have been a pizza restaurant, with three storeys of flats above it.
The incident took place at around 9.30pm local time.
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Belgium police do not know how many people were inside the building as rescue attempts carry on.
Antwerp police said: “The explosion on Paardenmarkt possibly involved three residences.
“There are multiple victims. The number is not known.”
Student Brett Buelens, who was in a building near the explosion told TV station VTM: “I heard people calling from under the rubble.
“I was sitting 40 metres away and I immediately came to see what had happened.
“There has been an explosion and there is a lot of damage up to the other side of the street.
“A building has been completely destroyed, two others are very damaged. I think it’s student rooms that have been destroyed.”
Police have said the explosion was not thought to be related to terrorism.
Police spokesman Wouter Bruyns said: “We ask people to make room in the surrounding streets for the emergency services that drive in and out.
“We also ask that the emergency centre is not overloaded with phone calls about this incident unless people are worried.”
Paardenmarkt is a busy road in the Belgian city, lined with restaurants and shops.
It is located near the city’s university and is popular with students.