It was unclear who was behind the bombing at the five-star Serena Hotel.
Police said rescuers took victims to nearby hospitals and footage on Pakistan news channels showed burning cars.
South-western Baluchistan province is the scene of a long-running insurgency by secessionist groups like the Baluchistan Liberation Front and the Baluchistan Liberation Army.
They have for decades staged attacks to press their demands for independence. The Pakistani Taliban also have a presence there.
Liaquat Shahwani, a provincial government spokesman, called the bombing an act of terrorism without elaborating. “Enemies of Pakistan are behind today’s attack,” he said.
Security forces rushed to the hotel and no one was being allowed to go near the site of the blast.
According to senior police official Azhar Akram, some of the wounded were in a critical condition.
Wasim Beg, a spokesperson at the provincial health department, said four people died and 12 were wounded in the bombing.
Arbab Kamran Kasi, a doctor at Quetta’s main hospital, said about a dozen wounded were being brought there and they declared an emergency at the hospital to handle victims.