The pontiff suggested that the middle finger, "which is higher than the others, reminds us of something essential: honesty."
It comes almost a decade after he resigned as the head of the Catholic Church.
The singer called out the Vatican's double standards, saying it was "happy to make a profit" from the story of his life.
Pope Francis has held his first general audience with a live crowd in six months, as restrictions ease after the coronavirus pandemic. About 500 people attended, nearly all of them wearing masks and keeping social distancing.