In his homily during the Mass that followed, Francis, who last month denounced the killing of 21 Egyptian Coptic Christians by Islamic State militants in Libya, said: "We think too of the humiliation endured by all those who, for their lives of fidelity to the Gospel, encounter discrimination and pay a personal price," he said, speaking in Italian.
"We think too of our brothers and sisters who are persecuted because they are Christians, the martyrs of our own time. There are many of them. They refuse to deny Jesus and they endure insult and injury with dignity," he said.
Earlier this month, the normally dove leaning Vatican said force may be necessary to stop attacks on Christians and other Middle East minorities by Islamic State if no political solution is found.
Francis clutched a palm frond for the religious service, celebrated outside St. Peter's Basilica.
In keeping with the simple tone of his two-year-old papacy, Francis leaned on a plain wooden pastoral staff instead of a traditionally more ornate one as he stood under a red canopy on the basilica steps.
Francis and other prelates at the Mass wore bright red vestments to recall Jesus' death by crucifixion. Tens of thousands of faithful held olive branches during Mass under blue skys over Rome.
Tourists and pilgrims have poured into Rome, with many expected to follow the pope's Way of the Cross service at the Colosseum on Friday.