The country's main Taliban faction claimed responsibility for the attack in the protected military zone of the northwestern city of Peshawar, saying it was their fourth reprisal for the U.S. killing of Osama bin Laden in Pakistan.
The bombing will likely highlight doubts about the security forces' ability to protect not only themselves, but major cities and fuel a long-running debate about the security of the country's nuclear weapons.
Militant unrest, much of it in the form of suicide attacks, has killed nearly 4,400 people in the past four years as the Taliban and militants linked to al-Qaida wage a bloody onslaught on Pakistan's U.S.-allied leadership.
Five policemen and a soldier died in Wednesday's explosion, a relatively low toll given the enormity of the blast, but officials said the building normally had only a skeleton staff at the time of the attack.
An Agence France Presse reporter saw flames from the stricken building, shattered glass on the ground, pancaked rubble, burning tyres and the charred remains of at least three vehicles, including a small truck.
Constable Farid Khan, who had his shoulder fractured in the attack and was admitted to a hospital told AFP that he was saying his morning prayers inside the police station when a deafening explosion took place.
"The roof of the building collapsed with the impact of the blast," he said, adding he could not get up because of his shoulder injury and his colleagues later took him to the hospital.
Rescuers were trying to reach four or five people believed trapped alive in the rubble, police official Muhammad Ijaz told AFP.
"It was a huge blast which completely destroyed the three-storey building," Ijaz added, saying there were usually 10 to 15 people present at that time in the police station.
Senior police official Shafiullah Khan said six people had died, after one policeman succumbed to his injuries in hospital and the body of another was pulled out of the rubble.
Police said another 23 people, including nine policemen and a child, were wounded in the blast in Peshawar, the gateway to the tribal belt on the Afghan border where U.S. drone strikes target Taliban and al-Qaida operatives.
The razed building housed the police Criminal Investigation Department and was located in the Peshawar Cantonment area just 150 meters from the U.S. consulate. The area houses military families and security is normally tight.
Police said the attack was carried out with a small truck containing at least 200-250 kilograms of explosives, and that body parts were hurled more than 300 meters away from the blast.
"We will further step up these attacks to avenge Osama bin Laden's martyrdom," Taliban spokesman Ehsanullah Ehsan told AFP by telephone from an undisclosed location.
"These attacks will continue until the U.S. drone strikes and ongoing Pakistani military operations are stopped in the tribal regions," he added.
The military rushed to seal off the area around the Peshawar police station after the 4:38 am (2338 GMT Tuesday) blast.
Last Friday, the Taliban bombed a U.S. consulate convoy, killing one Pakistani and wounding 11 other people in Peshawar, the first attack on Americans in Pakistan since bin Laden's killing in the town of Abbottabad on May 2.
Late on Sunday, heavily armed Taliban gunmen stormed a naval base in Pakistan's biggest city Karachi, destroying two U.S.-made surveillance planes and killing 10 personnel in a 17-hour standoff.
Following the brazen attack in Karachi, NATO chief Anders Fogh Rasmussen said Tuesday in Kabul that he was confident Pakistan's nuclear weapons were safe, but admitted the issue was a "matter of concern".
Tensions between the United States and Pakistan have run high since the al-Qaida mastermind of the September 11, 2001 attacks was killed.
However, the Pentagon said Tuesday that Pakistan had returned the wreckage of a U.S. helicopter that was damaged and deliberately destroyed during the raid.(AFP)