Khamenei made the remark during a meeting with Mauritanian President Mohammed Ould Abdel Aziz in Tehran, the website said.
The all-powerful Iranian leader also said that Israel's continued "pressure to erase Palestine from the world of Islamic nations" will fail.
"Surely, the day will come when the nations of the region will witness the destruction of the Zionist regime… when the destruction happens will depend on how the Islamic nations approach the issue," Khamenei told Aziz, who arrived in Tehran on Monday.
"The Zionist regime, by continuing to use pressure, blockades and committing genocide, wants to erase Palestine… but it will not succeed."
Praising Mauritania for cutting its ties with Israel, Khamenei said the "Zionist regime is a great danger to the world of Islam as it was thinking of expanding its influence and grip on the region every day."
Iranian officials, including Khamenei and President Mahmoud Ahmadinejad, have earned the wrath of Israel and Western powers for their repeated anti-Israel comments.
Relations between the two nations have deteriorated particularly under Ahmadinejad who has often said that Israel is "doomed to be wiped off the map" and has termed the Holocaust a "myth".
Israel shut down its embassy in Nouakchott following Mauritania's decision in January 2009 to suspend diplomatic ties with the Jewish state a decade after they were launched.
Mauritania was one of only three Arab nations that had formal diplomatic ties with Israel, apart from Egypt and Jordan.
