The Prime Minister says British jobs and businesses depend on being able to trade with Europe on a level playing field.
He's confirmed there will be no second referendum if the UK votes to leave the EU in June.
"I believe the choice is between being an even greater Britain inside a reformed EU or a great leap into the unknown," he said. "The challenges facing the west today are genuinely threatening. Putin's aggression in the east, Islamist extremism to the south - in my view, this is no time to divide the west.
"When faced with challenges to our way of life, our values and our freedoms, this is a time for strength in numbers."
Speaking on Premier's News Hour, the Prime Minister was backed by Christian Conservative MP Mark Pritchard.
He said: "My heart says to vote out, but my head and my intellect says we should remain in.
"For me, it's on national security grounds and geo-political reasons. I think we're safer in the European Union than out of it."
But Christian Conservative MP Sir Gerald Howarth isn't convinced.
Speaking on the News Hour, he said: "This is our chance to regain control of our country.
"To restore to our parliament the power to control our borders, the power to decide our laws for ourselves and so on."
Voters will get the opportunity to say whether they want the UK to leave or remain on June 23.
Listen to Mark Pritchard speaking to Premier's Hannah Tooley.
Listen to Sir Gerald Howarth speaking to Premier's Hannah Tooley.