Mohamad Rizal Buang, a senior fire officer in the southern state of Johor, told AFP the blaze at Johor Bahru's Sultanah Aminah Hospital, a public facility, had been contained after more than two hours.
"Six people were killed in the fire," he said.
Photographs posted on Facebook by the Malaysian health ministry's director-general Noor Hisham Abdullah showed black smoke billowing from the hospital's second floor and fire raging inside the building.
"I have been informed that there are victims due to the fire including patients and staff. A sad day for all of us," he said in an SMS message to AFP.
Noor Hisham also said one patient and two hospital staff are in critical condition due to smoke inhalation injuries and burns.
He said other patients were being sent to nearby hospitals, adding that "faulty wiring or a short circuit might be the cause but need to reconfirm."
Opened in 1982, the hospital is one of the busiest in Malaysia based on patient load.