A spokesperson for the ministry, in a statement carried by the official Saudi Press Agency, said nine other people were wounded, three of them in serious condition.
He identified three of those killed as "workers" in a mosque used by members of a Special Weapons and Tactics (SWAT) domestic security unit in Abha, in the southern province of Asir.
"The terrorist attack struck worshippers during prayer. Ten policemen and three workers were killed while nine were wounded, three seriously," the spokesman said.
He said the attack was likely carried out by a suicide bomber, saying that "body parts found at the scene" indicated the use of explosive vests.
State television El-Ikhbariya, which broke the news earlier, gave a death toll of 17.
It was too early to say who may have carried out the attack, an interior ministry spokesman told AFP.
Thursday's bombing was the most serious in recent months against Saudi security forces, who have been targeted in attacks blamed on the Islamic State group.
In mid-July, a car bomb exploded at a security checkpoint near a prison in the capital Riyadh. It killed the 19-year-old driver and wounded two policemen, the interior ministry said.
In the southwestern city of Taif on July 3, a policeman was gunned down during a raid in which three people were arrested and flags of the IS group found, police said earlier.
On successive Fridays in May suicide bombings at mosques of the minority Shia community in Eastern Province killed a total of 25 people.
An IS-affiliated group calling itself Najd Province - which takes its name from the region around Riyadh - claimed those attacks as well as another suicide bombing that killed 26 people at a Shia mosque in Kuwait in June.
The group considers Shias to be heretics.
IS claims responsibility
Meanwhile, the Islamic State group claimed responsibility for the suicide bomb attack.
The claim, made in an online statement by a group affiliated to IS calling itself "Al-Hijaz Province", said that one of its members detonated an explosive vest inside the mosque in the southern city of Abha.
Pakistan condemns mosque attack
Pakistan on Thursday strongly condemned the deadly terrorist attack at a mosque in Abha targeting security personnel.
“The people and government of Pakistan wish to convey their heartfelt sympathies and deepest condolences to the bereaved families and pray for speedy recovery of the injured,” a statement read.
Pakistan reiterated its condemnation of terrorism in all its forms and manifestations.
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