He did not specifically mention the planned withdrawal of 2,000 American troops from northern Syria, but in a televised speech in Damascus he said no one should bet on protection from the Americans.
He appeared to be referring to U.S.-allied Kurdish groups in the north who fear a Turkish assault once American troops withdraw from northeastern Syria. The U.S. has partnered with local Kurdish militias in the fight against the Islamic State group. The extremists are on the verge of territorial defeat in Syria and President Donald Trump has said he wants U.S. troops to leave Syria in the coming months.
Assad suggested the U.S. had sold out its Kurdish partners, and said that the Syrian army will return to the area after the American troop pullout.
"To those groups who are betting on the Americans, we say the Americans will not protect you... the Americans will put you in their pockets to be used as bargaining tools," he said.
"Every inch of Syria will be liberated, and any intruder is an enemy," Assad added.
Speaking confidently about the Syrian army's military advances on the ground, Assad called on refugees around the world to return to Syria.
The Syrian civil war, now almost eight years old, has left around 450,000 people dead and displaced half the country's population, including around six million outside the country.
Western countries and human rights organizations have said the security situation is not yet stable enough for their return, and the U.N. has said it cannot guarantee safety for those who do.
Without naming them specifically, Assad accused foreign countries of blocking the return of refugees.
"Syria is in need of all its sons and we call on refugees to return to take part in the process of reconstruction," Assad said.