But the latest comments marked Khamenei's first reaction since the idea of direct talks received a high-profile boost earlier this week from U.S. Vice President Joe Biden during a security summit in Munich attended by Iran's foreign minister.
Khamenei's statement also could spill over into the negotiations in Kazakhstan later this month between Iran and a six-nation group comprising the permanent U.N. Security Council members plus Germany. His apparent references to U.S. sanctions — saying Washington was "holding a gun" to Iran — suggests Iranian envoys will likely stick to demands for relief from the economic pressures before considering any nuclear concessions.
The U.S. this week further tightened sanctions on the Islamic Republic, which have already cut Iran's oil revenue by 45 percent. The new measures seek to cut deeper into Iran's ability to get oil revenue. It calls on countries that buy Iranian crude — mostly Asian nations including China and India — to set the money aside and require Iran use it buy local products rather than get cash.
"They say the ball is in Iran's court. The ball is in your court," said Khamenei. "You have to be accountable and explain what it means to offer talks while simultaneously continuing pressure and threats."
The comments followed another jab at the U.S.: Video broadcast on state TV purportedly from an advanced CIA spy drone captured in December 2011 after crossing into Iranian airspace from Afghanistan.
Iran has long claimed it managed to reverse-engineer the RQ-170 Sentinel, and that it's now capable of launching its own production line for the unmanned aircraft.
The video aired late Wednesday on Iranian shows an aerial view of an airport and a city, said to be a U.S. drone base and Kandahar, Afghanistan.
"We were able to definitively access the data of the drone, once we brought it down," said the chief of the Revolutionary Guard's airspace division, Gen. Amir Ali Hajizadeh, in the TV broadcast.
In an attempt to embarrass Washington, Iran has claimed to have captured several American drones, most recently in December, when Tehran said it seized a Boeing-designed ScanEagle drone — a less sophisticated aircraft — after it entered Iranian airspace over the Persian Gulf.
U.S. officials said there was no evidence that the latest claims were true.
Despite the tensions, American proposals for direct dialogue with Iran received a cautious welcome Sunday from Iran's Foreign Minister Ali Akbar Salehi. But he added caveats: Washington needs to quiet its "threatening rhetoric" for the offer to get real consideration by Tehran's ruling clerics.
All major decisions in Iran must be cleared by Khamenei, who has previously opposed direct negotiations with Washington and has shown no inclination of changing his positions.
"Talks will not solve any problems," Khamenei said in the statement posted Thursday following a meeting with air force commanders.
"You are holding a gun against Iran saying, 'Talks or you'll fire.' The Iranian nation will not be frightened by such threats," he added in apparent reference to U.S. sanctions over Iran's nuclear efforts.
Washington has indicated in the past that it's prepared to talk directly with Iran on the nuclear issue, but so far nothing has come of it. Meanwhile, the wider talks between Iran and world powers have made little headway. Three rounds last year ended in stalemate with Tehran pushing for a roll back of Western sanctions in exchange for any key concessions on its nuclear program.
The West and allies fear that Iran's uranium enrichment labs could eventually produce weapons-grade material. The Islamic Republic claims it only seeks nuclear fuel for energy reactors and medical applications.
The U.S. and Iran broke ties after the storming of the American Embassy in Tehran in the wake of the 1979 Islamic Revolution. Iranian militants held 52 American hostages for 444 days.
"I am not a diplomat. I am a revolutionary and I express my words honestly," Khamenei was quoted as saying.
He noted that some factions inside Iran seek the direct U.S. talks due to their "naivety." He did not elaborate, but called for the need to challenge U.S. efforts to return "domination" over Iran — a reference to the pro-Western shah that was toppled by the Islamic Revolution.
"Talk is meaningful if it is based on goodwill, equal standing and when both sides do not want to apply tricks," said Khamenei. "Talk as a tactic, a gesture of superpower, is only a deceptive move."
Khamenei, however, has shown some flexibility in the past over contacts with Washington. Iran and the U.S. have taken part in talks regarding Iraq and Afghanistan.