Speaking in Calabria, a region in southern Italy known to be a Mafia stronghold, Francis said organized crime group 'Ndrangheta was an example of "the adoration of evil and contempt for the common good."
"Those who in their life have gone along the evil ways, as in the case of the Mafia, they are not with God, they are excommunicated," the pope said.
"They must be told, 'No!' " Francis said, speaking before a crowd gathered at Piana di Sibari.
This isn't the first time Pope Francis has spoken out against the Mafia. In January he condemned a suspected Mafia killing that resulted in the deaths of a 3-year-old boy, Nicola "Coco" Campolongo, his grandfather, Giuseppe Iannicelli, and a third man.
"Let us pray with Coco, who is certainly with Jesus in heaven and for the people who carried out this crime, so that they repent and convert to the Lord," Francis said at the time.
During the pope's visit to Calabria on Saturday, he met with Coco's family.