"No one should see our negotiating team as compromisers," Khamenei, Iran's top decision-maker on its nuclear drive, was quoted as saying on his official website.
"I am not optimistic about the (nuclear) negotiations but, with the grace of God, we will not suffer losses either," he added.
A new round of talks between Iranian negotiators and representatives from the so-called P5+1 group of world powers is scheduled in Geneva for November 7 and 8.
The second meeting since moderate President Hassan Rouhani took office in August, the talks are aimed at curbing Iran's sensitive nuclear work in exchange for a relief from international sanctions strangling Iran's economy.
"All the better if the negotiations bear fruit but if there are no results, the country should rely on itself," said Khamenei while criticising the US policy of approaching the talks on two fronts of sanctions and diplomacy.
"The Americans smile and express desire for negotiation; on the other hand, they immediately say that all options are on the table," he said. "We should not trust a smiling enemy.
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