'We may face no greater challenge from a single country than from Iran,' Bush said in the National Security Strategy report to Congress, which is required every four years.
The United States has partnered with Britain, France and Germany to haul Iran before the UN Security Council in an effort to curtail its nuclear activities.
The Security Council began taking up the issue last week, but has not agreed on what steps should be taken to pressure Iran to comply with international demands to come clean on its nuclear programme.
'This diplomatic effort must succeed if confrontation is to be avoided,' said Bush, who has not ruled out military action to prevent Iran from acquiring nuclear weapons.
Iran says its nuclear work is purely to produce energy. The Security Council can impose sanctions, but facing resistance from Russia and China, the United States for the time being has opted to pursue a resolution outlining what Iran must do to satisfy the international community.
The report accused Iran of hiding its nuclear activities from the UN nuclear watchdog, the International Atomic Energy Agency (IAEA), and for failing to negotiate a solution to the dispute.
'The Iranian regime's true intentions are clearly revealed by the regime's refusal to negotiate in good faith; its refusal to come into compliance with its international obligations by providing the IAEA access to nuclear sites and resolving troubling questions,' the report said.
The report was published as Iran on Thursday said it wanted to hold direct talks with the United States on Iraq. The United States severed formal diplomatic relations with Iran after the seizure of the US embassy in 1979.
But the two countries have had informal contacts, namely through the Swiss, whose embassy in Tehran also represents the United States.
Last year Bush granted the US ambassador to Iraq, Zalmay Khalilzad, permission to hold talks with Iranian officials to explore ways to defuse tensions in Iraq. Khalilzad had had talks with the Iranians in Geneva in 2003 while he was still serving as the US envoy in Afghanisan.
Washington accuses Iran of meddling in conflict in Iraq by allowing weapons into the country.
The secretary of the Iranian National Security Council, Ali Larijani, said that Iran is ready to talk to the United States about Iraq. The United States had not yet responded to the proposal.
The National Security Report emphasized the importance of halting the spread of weapons of mass destruction and for promoting democracy.
'To end tyranny we must summon the collective outrage of the free world against the oppression, abuse, and impoverishment that tyrannical regimes inflict on their people - and summon their collective action against the dangers tyrants pose to the security of the world,' the report said.
It called on Hamas, which prevailed in January 25 Palestinian elections, to abandon terrorism and recognize Israel's right to exist.
'The Palestinian people having made their choice at the polls, the burden now shifts to those whom they have elected to take the steps necessary to advance peace, prosperity, and statehood for the Palestinian people,' Bush said in the report.
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