The holy week commemorating the last days of Jesus's life had a bloody beginning last Sunday with attacks claimed by the Islamic State group on two Coptic churches in Egypt that left 45 people dead.
Security was tight at the former gladiators' battle ground Friday, where a small group of believers were to carry a cross between 14 "stations" evoking the hours in the run-up to Jesus's crucifixion during the traditional Via Crucis (Way of the Cross) procession.
Three thousand officers have been deployed to protect the Colosseum, with road blocks and metal detectors in place and police helicopters with infrared systems surveying the area.
The pope is set to visit Egypt at the end of the month despite the church attacks.
The cross will also be carried for parts of the journey by believers from two other countries he will travel to this year: Portugal, which he will visit in May, and Colombia, where he heads in September.
Francis, 80, will sit under a canopy next to a large cross as he listens to a meditation written for the first time by a secular woman, French professor Anne-Marie Pelletier.
Good Friday is the second of four important days in the Christian calendar beginning with Maundy Thursday and culminating in Easter Sunday, which commemorates Christ's resurrection.
On Saturday, the pontiff will take part in an evening Easter vigil in St Peter's Basilica, before celebrating Easter mass on Sunday and pronouncing the traditional "Urbi et Orbi" blessing to Rome and the world.
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