Syrian state television said the explosion struck on the edge of a contested old neighbourhood in Aleppo. The television report identified the hotel as the Charlton hotel.
A local activist group called the Sham News Network also reported the blast, saying that President Bashar Assad's troops were based in the hotel.
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It said the hotel was completely destroyed in the blast and that there were casualties among the troops.
Aleppo, the country's largest city and former commercial hub, is carved up into rebel-held and government-held areas since the rebels launched an offensive there in mid-2010, capturing territory along Syria's northern border with Turkey.
In recent months, government aircraft relentlessly has bombed rebel-held areas of the city and the opposition fighters have hit back, firing mortars into government-held areas. The rebels also have detonated car bombs in residential areas, killing dozens of people.
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