It appeared a fire was set off deliberately in a school building housing security personnel at the state-run Cotabato Foundation College of Science and Technology, before the blast occurred Sunday night, police added.
"The fire drew responders, including firemen, teachers, and students, and they were among the injured,'' explained Senior Inspector Rolly Oranza of the local police force in the troubled Mindanao region.
He said 17 of the wounded remain in a critical condition at the hospital.
Police told AFP they believe the explosion was caused by an improvised explosive device, but ordnance experts were still determining the details.
No group had claimed responsibility for the attack, and police were still trying to determine the motive, Inspector Oranza said.
The school is situated in Arakan, a quiet farming community on the southern island of Mindanao, populated mostly by indigenous tribes.
Mindanao is gripped by a long-running Muslim insurgency that has left more than 150,000 dead.
While Muslim rebels are not known to operate in Arakan, there has been violence between armed paramilitary groups fighting for control of the area.
Communist rebels are also known to have some presence in Arakan, but police said it was unclear if they were involved.
In October 2011, an Italian Catholic priest who had been helping tribal groups was shot dead as he was leaving his parish in Arakan.
In September, Insp Oranza said, police defused an improvised bomb planted near the school's flagpole.