Ten fire engines and around 70 firefighters were called to a fire on Pepper Street on the Isle of Dogs.
The fire was situated within a ground-floor restaurant, which has flats above. Several people inside the restaurant and in the flats above left the building before firefighters arrived. There were no reports of any injuries.
The fire was producing a heavy amount of smoke in the local area and people were advised to keep their windows and doors closed.
Station Commander Chris May, who was at the scene, said: "The fire caused heavy smoke logging throughout the block of flats above and firefighters wearing breathing apparatus carried out a systematic search of the building to ensure everyone is accounted for. Crews also ventilated the building."
Due to smoke travel, Crossharbour DLR station was temporarily closed but reopened later on in the evening.
The Brigade received the first of four calls at 1616 and Control Officers mobilised crews from Millwall, Whitechapel, Plaistow, East Greenwich and surrounding fire stations to the scene. The fire was brought under control by 1821.
The cause of the fire is under investigation.