Only Greenland and Denmark must decide the future of Greenland, Prime Minister Sir Keir Starmer has told the BBC.
It comes after President Trump again said "we need Greenland from the standpoint of national security".
The US president and senior members of his administration have repeatedly raised the prospect of the semi-autonomous Danish territory becoming an annexed part of the United States.
Both Greenland's prime minister and Denmark's prime minister strongly rejected the idea over the weekend.
Greenland's Prime Minister Jens Frederik Nielsen responded to Trump's latest comments by saying "that's enough now" and described the notion of US control over the island as a "fantasy".
Meanwhile, Denmark's Prime Minister Mette Frederiksen had said "the US has no right to annex any of the three nations in the Danish kingdom".
Asked whether he would also say to President Trump "hands off Greenland", Sir Keir's response was definitive, when so often in diplomacy answers are caveated and nuanced.
"Yes," he replied. "Greenland and the Kingdom of Denmark must decide the future of Greenland and only Greenland and the Kingdom of Denmark.
"And Denmark is a close ally in Europe, is a Nato ally and it is very important that the future of Greenland is for the Kingdom of Denmark and for Greenland themselves and only for Greenland and the Kingdom of Denmark."
The prime minister's language on the legality or otherwise of America's seizing of the Venezuelan President and his wife in recent days was considerably less definitive.
"The US will have to justify the action it has taken," Sir Keir said, adding that "we will always defend the international rule of law".
But he repeatedly ducked offering a straight answer as to whether the US had acted within international law.
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