"Iran and the Islamic state want to destroy us, and a hatred for Jews is being directed towards the Jewish state today," he said at a ceremony in Jerusalem's Yad Vashem memorial.
"Those who threaten to destroy us risk being destroyed themselves," Netanyahu warned.
"From being defenseless people, we have become a state with a defensive capacity that is among the strongest in the world," he said.
Six Holocaust survivors lit torches in memory of the six million Jews killed by the Nazis during the 1939-1945 World War II.
'Holocaust is happening in Syria' says Israel's former chief rabbi
Israel will also come to a standstill for two minutes at 10 am local time on Thursday as sirens wail in remembrance of the Jewish victims of Nazism.
Radio stations and television channels on Sunday were broadcasting programmes about the genocide.
More than 213,000 Holocaust survivors live in Israel today, many of them below the poverty line, according to survivors' groups.
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