About 500 guests had to be evacuated following the blast at The Churchill Hyatt Regency hotel shortly before midnight on Friday, London Fire Brigade said.
Five of the injured required hospital treatment, including two men with leg wounds, London Ambulance Service added.
It was unclear if the injured were hotel guests.
"The explosion was in the hotel basement which has caused extensive damage to the basement and the ground floor. Five cars in a neighbouring street were also damaged," the fire brigade said. "The cause of the explosion is being investigated but is believed to have been caused by a suspected gas leak."
The workers from the National Grid energy network company are investigating the incident.
The Churchill on Portman Square has 434 rooms and suites with an average daily rate of £264 per room per night.
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