The escalating violence has raised fears of wider sectarian conflict in a country reeling from months of attacks on churches, government buildings and other sites by the Islamist Boko Haram sect.
The movement styled on the Taliban appears bent on provoking Christian-Muslim clashes as part of its campaign to carve an Islamic state out of parts of Nigeria.
At least 40 people were killed in clashes between Muslim and Christian residents in the northern city of Kaduna on Tuesday, triggered by the suspected Islamist bombings of three churches, according to figures from a Nigeria Red Cross official.
"I am following with deep concern the news from Nigeria, where terrorist attacks are continuing especially against Christians," the pope said at his weekly general audience.
"I appeal to those responsible for the violence to immediately stop the spilling of the blood of many innocents."
He urged all groups in Nigeria to shun "the path of vendetta" and work towards building a peaceful society where people were free to practise their religion.