The attack occurred as the minority Shia community observed their holiest day of Ashura.
The bomb, planted in a shop in Chogla area of Dera Ismail Khan, was triggered by remote-control as a procession was passing by.
A security personnel was among the five persons killed in the attack, Khyber-Pakhtunkhwa Information Minister Mian Iftikhar Hussain said.
Four security personnel, women and children were among the injured.
Several of the wounded were in a critical condition.
Yesterday, eight persons were killed and about 20 injured when another Shia procession was targeted with a roadside bomb in Dera Ismail Khan.
The banned Tehrik-e-Taliban Pakistan claimed responsibility for both bombings in the city as well as a suicide attack on a Shia procession in Rawalpindi that killed 23 people and injured over 60 on Wednesday.
Authorities called in army soldiers to patrol the streets of Dera Ismail Khan after the attacks.
The bombings caused widespread panic in the city.
Tehrik-e-Taliban Pakistan spokesman Ihsanullah Ihsan told the media that his organisation had carried out today's attack.