Iran and the United States have had no diplomatic relations since the takeover of the US Embassy in Tehran on November 4, 1979, when militant students stormed the compound and took 52 Americans hostage for 444 days.
Ayatollah Ali Khamenei, while meeting with Iranian students ahead of the anniversary of the takeover, said the "aim of the slogan is not death to American people. The slogan means death to US policies and arrogance."
Even after 36 years, the slogan still has "strong support" in Iran, he said.
Current President Hassan Rouhani has made efforts to improve relations, including a landmark nuclear agreement reached with world powers this past summer.
While Khamenei has thrown his weight behind the nuclear deal – which lifts sanctions in exchange for curbing Iran's nuclear program – he remains deeply suspicious of the United States and said it is not be trusted.
Khamenei believes that the US "will not hesitate" if given a chance to destroy Iran.
"The nature of the US attitude is continuation of the same hostile aims from the past, and the nation will not forget this," he said.