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 residents left the building before firefighters arrived. There have been no reports of any injuries at this time.
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 has been at the scene, said: "The fire is under control but firefighters remain on scene fully extinguishing any hotspots.
"The fire caused heavy smoke logging throughout the block of flats above and firefighters wearing breathing apparatus have carried out a systematic search of the building to ensure everyone is accounted for. Crews have also ventilated the building."
Due to smoke travel, Crossharbour DLR station was temporarily closed.
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.