For long time, the Italian Mezzogiorno region has been identified as: the land of popular religion; the place of reproduction of ancient beliefs; a region in which a centrality of Catholic commitments and the Church was present. At the same time, the excessive ritualism and the popular cult of the Saints has been study parallel to the concept of paternalismo notabilare and with mafia organizations’ capacity to penetrate both institutions and the cultural and social local fabric. The aim of this article is to discuss continuities and changes of these distinctive traits of religiosity in Southern Italy. After a historical overview of the way in which the attention of the Roman Catholic Church towards Mezzogiorno has changed from the end of 1880s to now, as well as of the challenges that the Church of South has faced, two issue will be discussed. On one hand, the changing role of the Roman Catholic Church and of the Church of the South in the face of the Mafia will be discussed. Particular attention will be given to the new role of vigilance of the popular religious festivities, historically controlled by the criminal organization. On the other hand, through the use of survey data, continuities and changes in the Southerners’ image of the Church will be analyzed. In conclusion, starting from previous analyses, the central role Catholic religion continues to have in Italian Mezzogiorno will be underlined and discussed.