A major incident has been declared, after local echo24.cz reported that Prague firefighters fought an inferno in a four-star hotel on Naplavni Street, an area popular with tourists.
Some 40 are thought to have been injured, as the death toll is expected to rise during a search of the Eurostars David hotel.
Prague Emergency Medical Service head Petr Kolouch stated: "There are two deaths but we are afraid that won't be the final figure," cited by Express.co.uk.
"Three people were resuscitated," Kolouch said, adding, "One has already managed to restore circulation.'"
Beginning on the hotel's ground floor, the cause of the fire is as yet unknown.