Ten fire engines and about 70 firefighters were called to the blaze in Channel Close, Hounslow, at 10.26pm on Sunday, London fire brigade said.
The ground floor and first floor of the mid-terrace house were destroyed by the fire and part of the roof was also damaged.
Five people on the first floor of the building were pronounced dead at the scene, the brigade said.
The Metropolitan police said three children were thought to have died in the blaze and that those killed were all believed to be members of the same family.
One man left the property before emergency crews arrived and was later taken to hospital with injuries that were not life-threatening. One person remained unaccounted for.
The Met said the cause of the fire was under investigation but no arrests had been made.
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