The brief visit, which will see the 81-year-old pontiff stay on the Italian island until evening, is part of a wider campaign he has been waging against organised crime.
“You can't believe in God and belong to the mafia. Those who belong to the mafia don't lead a Christian existence because their lives are blasphemous,” he said at an open-air mass near Palermo's port, where some 100,000 had gathered according to official estimates.
“Change! Stop thinking about yourselves and your money, convert!” His impassioned plea echoed the words of Jean Paul II who during a May 1993 trip to the island had also called on mobsters to abandon crime and urged Sicilians to revolt against the mafia.
The mobsters responded two months later with attacks on two Catholic churches.
Saturday's homily was held in honour of Father Giuseppe “Pino” Puglisi, who served as parish priest in the rough Palermo neighbourhood of Brancaccio for two years, trying to engage local youngsters and keep them away from drugs and the mafia suppliers.
But on September 15, 1993 — his 56th birthday — he was shot dead at point-blank range.
“I was waiting for you,” he reportedly said with a smile before dying on the doorstep of his modest home in Brancaccio, a neighbourhood Francis will visit after celebrating mass.
His murder came as Italy was still reeling from the killings of two anti-mafia judges.
In 2012, Pope Benedict XVI officially recognised Puglisi as a martyr, “killed by hatred of the faith”.
The following year he was beatified, in the first step on the path to sainthood within the Roman Catholic church.
Since becoming pope in 2013, Francis has openly confronted the mafia and called on the faithful to stop all collaboration with them.
Mafiosi are often practising members and benefactors of Catholic parishes. Prior to arriving in Palermo, Francis stopped in Piazza Armerina, a small impoverished town in central Sicily.
“The wounds which afflict you are many, and they have a name: social and cultural under-development, the exploitation of workers and a lack of decent work for young people,” he said to widespread applause.
Although he didn't mention organised crime, he spoke about “extortionate money-lending” and “gambling”.
During a 2015 address in Naples, the notorious fiefdom of the country's oldest organised crime syndicate the Camorra, Francis had also condemned those “who exploit and corrupt young people, the poor and the disadvantaged”.
In Calabria, another Cosa Nostra hotspot in southern Italy, he had called on Catholics to combat the local mob, known as the 'Ndrangheta.
“Those who in their lives follow this path of evil, as the mafiosi do, are not in communion with God,” he said, declaring them “ex-communicated” to thunderous applause from the 100,000-strong crowd.
Ex-communication is the severest penalty for Catholics, banishing them from the spiritual life and sacraments of the church.
Taking a stand
Local bishops have already ex-communicated mafia members but the Vatican is considering creating a new doctrine ex-communicating organised crime group members worldwide.
Despite the papal rhetoric, relations between the church and organised crime groups have often been ambiguous, with mafia types trying to bribe or influence priests, the misappropriation of resources from institutions and charities, and questions over the purchase of Vatican real estate. But some local bishops are taking a stand.
Last year, the bishop of Monreale, near Palermo, made headlines by criticising a priest who had allowed the son of one of Sicily's most notorious mobsters, Toto Riina, to act as godfather at a baptism.
And in 2016, a priest in southern Italy who had wanted to hold a mass in memory of a 'Ndrangheta mafia boss was taken to task by the mayor, the archbishop and his parishioners.