Trump told an interview he was protestant but had "great respect" for the pontiff and would be keen to meet him during his visit to America next month.
Asked by CNN how he would respond to the Pope's view that capitalism can cause social injustice and climate change he replied: "I'd say, 'Isil [Islamic State] wants to get you'".
He added: "You know that Isis [Islamic State] wants to go in and take over the Vatican... I'm going to have to scare the Pope because it's the only thing.
"The Pope, I hope, can only be scared by God.
"But the truth is - you know, if you look at what's going on - they better hope that capitalism works, because it's the only thing we have right now. And it's a great thing when it works properly."
He added: "I don't think the Pope is opposed to capitalism, I've seen a lot of the things he's opposed to and I don't think the Pope is opposed to capitalism."
Pope Francis has previously suggested the pursuit of money was "the dung of the devil" and urged poor countries not to be used for cheap labour for developed nations.