The North "will never allow any human rights dialogue or nuclear one with the enemy keen to overthrow it", a foreign ministry spokesman said through the official Korean Central News Agency.
The idea of denuclearising the Korean peninsula has become "totally meaningless" due to the US policy of trying to bring down North Korea and its social system over human rights issues, he said.
"It is self-evident that one party cannot discuss its unilateral disarming with the rival party keen to bring it down at any cost," the spokesman said.
The aid-for-denuclearisation talks involving both Koreas, China, the US, Russia and Japan have been stalled since 2009.
Recently the North has stepped up a diplomatic offencive aimed at neutralising a proposed United Nations resolution requesting that it be referred to the International Criminal Court for possible prosecution.
A draft resolution to be presented soon by the European Union and Japan to the UN General Assembly is expected harshly to condemn rights abuses in the North, based on the findings of a UN report.
In the past the totalitarian regime had refused to discuss rights issues. But in recent weeks it has held rare UN briefings, ostensibly in a bid to counter growing global criticism.
Last week North Korean officials held a meeting with Marzuki Darusman, the country's first for 10 years with a UN rights investigator. They offered to host UN envoys.
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