London Fire Brigade said the hotel was suffering from an inferno, with the building's ducting in its extraction system on fire.
It said in a statement: "Four fire engines and around 25 firefighters have been called to a fire at a hotel and restaurant on Chiltern Street in Marylebone.
The fire brigade has been called at 2.52pm, with fire crews from Soho, Euston, and Paddington attending the scene.
"Fire crews from Soho, Euston and Paddington fire stations are at the scene.
London Fire Brigade added: "The Brigade was called at 1452.
