"Iran's nuclear technology is non-negotiable and comments about Iran's nuclear facilities are worthless and there is no need to negotiate or hold talks about them," said Zarif, reacting to the remarks of the US top diplomat in the nuclear talks, ISNA news agency reported.
"Those who know our peaceful objectives are also aware that we will not negotiate about our (nuclear) facilities," Zarif added.
Wendy Sherman, who is spearheading diplomacy with Tehran on its nuclear programme, said Iran did not need some of its nuclear facilities.
Iran struck an interim nuclear deal in November, under which it agreed to roll back parts of its nuclear work in exchange for the release of billions of dollars in frozen assets and limited relief from sanctions that have choked its economy.
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It also committed not to make further advances at its Arak, Fordo and Natanz facilities.
Fordo is an underground nuclear enrichment facility with nearly 3,000 centrifuges and dug deep into a mountain near the Shiite holy city of Qom, some 150 kilometres south of Tehran.
Western powers suspect Iran's nuclear activities mask military objectives, despite repeated denials from Tehran, which insists its programme is entirely peaceful.
"Ms Sherman should stick to the reality and stop speaking of impossible things even if it is only for domestic consumption ... Since reaching a solution can be hindered by such words," said Zarif.
Talks between Iran and world powers aimed at reaching a comprehensive nuclear agreement are to resume on February 18 in Vienna, following November's interim deal.