"The first US shot on Iran would set the United States' vital interests in the world on fire," said Ali Shirazi, an aide to Iran's supreme leader.
"Tel Aviv and the US fleet in the Persian Gulf would be the targets that would be set on fire," he said.
Tehran denies Western claims that it is seeking to build a nuclear weapon.
It has repeatedly rejected demands to halt enriching uranium, which can be used as fuel for power plants or material for weapons if refined to a greater degree.
The European Union imposed new sanctions on Iran in June.
But it has offered a package of incentives to persuade Iran to suspend uranium enrichment.
Iran has said it is prepared to negotiate with major world powers, but insisted the talks must address Iran's nuclear rights.
Ali Shirazi is a cleric working as representative of Supreme Leader Ayatollah Ali Khamenei to the naval unit of Iran's elite Revolutionary Guards.
His comments come amid reports of possible US or Israeli plans to strike Iran's nuclear facilities.
"The Zionist regime is pressuring White House officials to attack Iran. If they commit such a stupidity, Tel Aviv and US shipping in the Persian Gulf will be Iran's first targets and they will be burned in Iran's crushing response," Mr Shirazi was quoted as saying by Iranian news agencies.
"The Iranian nation will never accept bullying. The Iranian nation is a nation of believers which believes in jihad and martyrdom. No army in the world can confront it," he said.
Last week, the top US military officer said opening up a new front in the Middle East - after Iraq and Afghanistan - would be "extremely stressful" for US forces.
Adm Mike Mullen, chairman of the Joint Chiefs of Staff, was commenting on the likelihood of US or Israeli military action over Iran's nuclear programme.President George W Bush has maintained that all options are on the table but that military action against Iran will not be his first choice.
I don't want it, but it's coming....