Azhar Ikram, a senior police official in the city, confirmed the death toll and said that the Chinese ambassador was staying at the hotel, but was not present at the time of the blast.
The separatists in the region accuse the government and China of exploiting Balochistan, one of Pakistan's poorest provinces, for its gas and mineral wealth - with, they say, little benefit to local people.
He added that despite the security measures, the vehicle carrying explosives managed to enter the parking lot from the main gate of the hotel, which is a matter of big concern and the people responsible will be taken to task for a security lapse.
It was unclear who was behind the attack.
He said the investigation into the bomb blast will take note of loopholes.
The hotel is in Quetta, the capital of southwestern Balochistan province that has always been the scene of low-level insurgency from local nationalists. He provided no further details, saying police were still investigating.
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Four people were reported to have been killed, including two security guards, and a dozen more were said to have been injured.
"A vehicle that was full of explosives exploded in the hotel", Pakistan's Interior Minister Sheikh Rashid Ahmad told local ARY News TV.
No one immediately claimed responsibility for the attack in the provincial capital.
Liaquat Shahwani, a provincial government spokesman, called the attack an act of terrorism.
Balochistan Inspector General Muhammad Tahir Rai told the media that neither the Chinese ambassador nor other members of any foreign delegation were staying at the hotel when the blast occurred.
Pakistan has almost completed a fence along the border with Afghanistan, which Islamabad says is necessary to prevent militant attacks from both sides.