"I am very optimistic about the future of Palestine and believe Israel is on the steep path of decline and deterioration," Khamenei told Ramadan Abdullah, the secretary general of Palestinian militant group Islamic Jihad.
"God willing, its destruction will be imminent," the Islamic republic's all-powerful leader said. "Continued resistance and hope for victory should be taken into consideration."
Iran does not recognise Israel, and is a staunch backer of Palestinian Islamist militants.
Tensions have soared between Iran and Israel over the past five years since hardline President Mahmoud Ahmadinejad came to power.
Ahmadinejad has drawn international condemnation by repeatedly predicting that Israel is doomed to disappear and dismissing the Holocaust as a "myth."
Israel, the sole if undeclared nuclear power in the Middle East, has called for tougher action against Tehran over its controversial atomic programme and accuses it of seeking nuclear weapons, a charge Iran denies.
