Several others have been injured and the death toll is expected to rise.
Mogadishu truck bomb: Blast in Somali capital kills at least 20
At least 20 people have died after a truck bomb detonated in a busy street in Mogadishu, Somalia, police said.
Several others have been injured from the blast in the Somalian capital, which took place in an area surrounded by government offices, hotels and restaurants.
"Initial reports from emergency departments indicate more than 20 bodies picked up off the street and many more are under the wreckage of buildings destroyed by the blast," said Ibrahim Mohamed, a senior police officer.
No one has yet claimed responsibility for the attack, but Somalia has been fighting a war with the insurgent group Al Shabab. The Al Qaeda-linked insurgents, who were largely forced out of Mogadishu by military operations in 2011, have carried out frequent suicide bombings in the capital.
The blast sent a thick cloud of smoke into the sky that could be seen across the city, badly damaged a nearby hotel and left scenes of devastation near the "Kilometre 5" intersection.
Emergency services were overwhelmed as they sought to respond to the bombing.
"The emergency team don't even know how many people they have collected because of the high number of the casualties," said Abdukadir Haji Aden, director of Mogadishu's main Amin Ambulance Service.
"They have collected tens of dead and injured and the work is still ongoing."
The so-called K5 junction is in the Hodan district, a bustling commercial part of the city with many shops, hotels and businesses.
The explosion occurred outside the Safari Hotel, a popular place but not one that is commonly used by government officials. It is not known whether the hotel was the target on this occasion, but in the past Al Shabab has frequently attacked hotels where officials stay.
Witnesses described horrific scenes after the explosion.
"This was very horrible, the bomb went off alongside the busy road and left many people dead. I saw several dead bodies strewn about but could not count them," said Ismail Yusuf.
Muhidin Ali, a Mogadishu resident, said it was, "the biggest blast I have ever witnessed, it destroyed the whole area".
"There were dead bodies everywhere and injured people were screaming, some of them from under the rubble of destroyed buildings," said Fadumo Dahir.
"The whole area looks like a scene from a war," said Ahmed Bare, another witness.
Al Shabaab was forced out of the capital six years ago by African Union and Somali troops, and subsequently lost control of major towns across southern Somalia.
However, the militants continue to control rural areas and launch attacks on military, government and civilian targets in Somalia, as well as terrorist raids in neighbouring Kenya.
Saturday's blast came two days after Somalia's defence minister and army chief both resigned without explanation.