The Argentine pontiff will visit the Sanctuary of Our Lady of Fatima north of Lisbon, a site which marks six reported apparitions of Mary to child shepherds a century ago.
It is believed the mother of Jesus appeared in Fatima to three youngsters on six occasions between May and October 1917.
Fatima Shrine
The pope is due to arrive on Friday before he marks the 100th anniversary of the first reported apparition by declaring on Saturday two of the youngsters - siblings, Jacinta and Francisco - saints.
The pair, who died during childhood, have been linked to two miracles.
Carmo Rodeia, one of the sanctuary managers at the site, was quoted by AFP as saying 40,000 walkers, 2,000 journalists, 2,000 clergy and 350 patients hoping for healing will attend the pope's visit.
Francis will be among four pontiffs to have visit the site in half a century.