"To resign would be to flee," he told the Clarin when asked if he would consider stepping aside as called for by US Secretary of State John Kerry.
"I don't know if Kerry or anyone else has received the power of the Syrian people to talk in their name about who should go and who should stay. That will be determined by the Syrian people in the 2014 presidential elections," Assad said.
Assad spoke to Clarin and the Argentine state news agency Telam in a lengthy interview in Damascus in which he also denied that his government has used chemical weapons against the civilian population.
His comments come amid a rare joint push by the United States and Russia to convene a peace conference in Geneva that would bring together members of the regime and the rebels fighting to oust Assad.
"We have received the Russian-US approach well and we hope that there will be an international conference to help Syrians overcome the crisis," Clarin quoted Assad as saying.
He added, however, that "we do not believe that many Western countries really want a solution in Syria. And we don't think that the forces that support the terrorists want a solution to the crisis.
"We must be clear," he said. "There is confusion in the world over a political solution and terrorism. They think that a political conference will stop terrorism on the ground. This is unrealistic."
Pressure for action on Syria has mounted with Western intelligence reports that the regime has used chemical weapons on at least two occasions and a death toll nearing 95,000 after 26 months of war, according to a Syrian observer group.
Telam quoted Assad as denying that his government has used chemical weapons against its civilian population, saying that mass casualties could not be hidden if the regime had.
"The accusations against Syria regarding the use of chemical weapons or my resignation change every day. And it is likely that this is used as a prelude to a war against our country," he said.
"They said we use chemical weapons against residential areas. If they were used in a city or a suburb with only 10 or 20 victims, would that be credible?"
Their use, he said, "would mean the death of thousands or tens of thousands of people in a matter of minutes. Who could hide something like that?"
Assad also questioned the estimates of the number of dead produced by human rights groups, but acknowledged that "thousands of Syrians have died."
"We shouldn't ignore that many of the dead that they talk about are foreigners who have come to kill the Syrian people," he said, blaming "local terrorism and that coming from abroad" for the violence.
Clarin said Assad denied that his government was using "fighters from outside of Syria, of other nationalities, and needs no support from any Arab or foreign state.
"There are Hezbollah people in Iran, in Syria, but they come and go in Syria from long before the crisis," he said.