The shelter is under construction on Via Penitenzieri, just a few steps away from the Vatican walls, a Holy See spokeswoman said.
Once completed, the centre will be run by volunteers, who will host 30 people at a time.
Setting up a shelter is just one of a few initiatives by Pope Francis to highlight the suffering of homeless people in the Italian capital.
Earlier this month, the pontiff donated money for two busloads of poor people to travel from Rome to see the Shroud of Turin, a cloth some believe Jesus was wrapped in after he was crucified. The Pope will visit Turin on June 21 to see the shroud himself.
In March, Francis invited some 150 mostly homeless people to a private viewing of the Vatican museums and the Sistine Chapel.
And in February, he asked that showers be set up for homeless people under the colonnade of St. Peter’s Square. The Vatican’s charity office began offering haircuts and shaves by professional volunteers, as part of the shower service.
Of course, Francis is not the first pope to reach out to the poor and homeless. Mother Teresa persuaded St. John Paul II to open a soup kitchen and homeless shelter just inside the Vatican walls in the 1980s.
But Francis has consistently called on Catholics to create a “poor church,” elevating the theme of poverty among his signal initiatives. Addressing followers in St. Peter’s Square on June 3, Francis praised the dignity of poor families, who he said could “save society from barbarity.”