The US called on Iran to withdraw its forces from Syria as part of conditions to lift new sanctions
Syrian Deputy Foreign Minister Faisal Mekdad said on Wednesday that the withdrawal of Iranian forces from Syria was "not up for discussion", Lebanon's al-Mayadeen TV reported.
"Whether Iranian forces or Hezbollah withdraw or stay in Syria is not up for discussion because it's the (business) of the Syrian government," the channel cited him as saying.
Washington has demanded Iran make sweeping changes - from dropping its nuclear program to pulling out of the Syrian conflict - or face severe economic sanctions.
Speakig on Monday, US Secretary of State Mike Pompeo outlined a list of 12 points, including withdrawing forces from Syria.
"Iran will be forced to make a choice: either fight to keep its economy off life support at home or keep squandering precious wealth on fights abroad," said Pompeo.
"It will not have the resources to do both."
US President Donald Trump has long said the original 2015 nuclear deal with Iran, which was also signed by Britain, China, France, Germany and Russia, did not go far enough, and now wants the Europeans and others to support Washington's hardline strategy.
"In the strategy we are announcing today, we want the support of our most important allies and partners in the region and around the globe. I don't just mean our friends in Europe," Pompeo said.
The secretary of state also said that European businesses who work with Iran in violation of US sanctions would be held "to account".
The re-establishment of US sanctions is likely to force European companies to choose between investing in Iran or trading with the United States.
The European Union is currently trying to persuade Iran to stay in the 2015 deal, even without Washington's participation.
On Friday, the European Commission proposed that EU governments make direct money transfers to Iran's central bank to avoid US penalties, a step which would bypass the US financial system.