Saudi newspapers have accused the powerful "mutaween" police of hindering attempts to save 15 girls who died in the fire on Monday because they were not wearing correct Islamic dress.
Prince Nayef said the reports were untrue and the religious police were only there to ensure that the girls were not subjected to any mistreatment once outside the school.
The incident has caused an unprecedented outcry in Saudi Arabia, where public criticism of the religious police is rare.
Feared force
The mutaween - or Commission for the Promotion of Virtue and Prevention of Vice - are widely feared in Saudi Arabia. They roam the streets enforcing dress codes and sex segregation, and ensuring prayers are performed on time.
About 800 pupils were inside the school in the holy city of Mecca when the tragedy occurred. More than 50 were injured in the incident.
Prince Nayef said that two members of the police force had gone to the scene of the fire to "ensure that the girls were not subjected to any kind of mistreatment outside the building".
They "did not interfere in any other matter," he said in an interview with Monday's Arab News, a Saudi government-controlled daily.
Differing accounts
Prince Nayef said newspapers had rushed to report "news which turns out to be untrue".
"What has been said about the men of the commission was totally baseless," Prince Nayef was quoted as saying.
Earlier the director of the religious police, Sheik Jaber al-Hakmi, denied his officers had prevented rescuers from entering the school.
But the head of Mecca's police, Mohammed al-Harthy, said that when he arrived at the fire he found a member of the religious police "trying to interfere".
"He was fighting with a police officer, trying to prevent him from entering the school," Mr al-Harthy said.