Iran has suggested it could curb its highest-known level of uranium enrichment - at 20 percent - in a possible deal that could ease the US-led economic sanctions.
But Iranian leaders have made clear that their country will not consider giving up its ability to make nuclear fuel - the centrepiece of the talks since the same process used to make reactor stock can be used to make weapons-grade material.
Khamenei said he would not "interfere in the details of the talks," - a clear nod of support for the government of Iranian President Hassan Rouhani, which has opened historic exchanges with the US However, Khamenei also said the main goal of the talks is the "stabilisation of the rights of the Iranian nation, including nuclear rights."
"There are red lines. There are limits. These limits must be observed," the supreme leader told the Basij force, which is controlled by Iran's powerful Revolutionary Guard. "We have told the authorities, and they are required to observe the limits and should not fear the blusters of the enemies and opponents."
Khamenei also blasted what he called the US government's "warmongering" policies, including threats of military action, and he said sanctions cannot force unwanted concessions by Iran. At the same time, Khamenei said his country has "no animosity'" toward the American people and seeks "friendly" relations.
"Instead of using threats, go and repair your devastated economy so that your government is not shut down for 15 or 16 days," he said, referring to the recent US government closure amid a congressional budget standoff. "Go and pay your debts."
His complex message reflected Iran's internal divisions over the nuclear talks and outreach to the United States, which broke ties with Iran after hostage-takers stormed the US Embassy compound in Tehran in 1979 the wake of the Islamic Revolution.
President Barack Obama also faces opposition to a deal from Israel, Saudi Arabia and critics in the US Congress, who say an first-step deal would give Iran too much in the way of sanctions relief for too little concessions. They also argue that Iran can't be trusted.
Obama and his national security team have countered that the risk is worth taking because the alternative is war no one wants.
On Wednesday, delegations arrived in Geneva for internal consultations ahead of a full round of talks between Iran and six nations: the US, Russia, China, Britain, France and Germany.
- AP