The Cabinet Office Minister, who previously served as Britain’s chief Brexit negotiator, made the warning at a British-Irish Association conference held in Oxford. Under the terms of the protocol, some checks now take place on trade between Northern Ireland and the rest of the UK.
This has infuriated unionists, who argue it undermines their British identity.
Lord Frost argued the protocol is key to EU-UK tensions and is undermining a potentially cooperative relationship.
In his speech, Lord Frost insisted the UK will resolve the issues despite the EU’s threats.
He said: “You should be in no doubt about the centrality of this problem to our politics and to this Government.
“The issue needs to be fixed and we are determined to fix it.
“It is, as the PM made clear to allies at the G7 Summit, inseparable from our view of our own territorial integrity and of what is best for Northern Ireland in the decades ahead.
“It is important everyone grasps the opportunity, looks at the risks of not doing so, and acts constructively.
“We are absolutely ready to do so.”
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However, some Brexit supporters are calling for it to be scrapped altogether.
Lord Frost added: “The current governance arrangements have to evolve to reflect the reality that this is an agreement between two sovereign and autonomous entities, not a relationship of subordination or one where one party’s rules have to be applied mechanically by the other.
“You should be in no doubt about the centrality of this problem to our politics and to this Government.
“The issue needs to be fixed and we are determined to fix it.”
Whilst Britain formally left the EU in January 2020, it remained closely tied to the bloc until December during the Brexit transition period.
At this point Boris Johnson’s new Brexit trade deal took effect, restoring the UK as a fully independent trading nation.
However, this also contained the controversial Northern Ireland protocol which infuriated unionists.
Tensions remain high in Northern Ireland ahead of assembly elections, which are due to take place next May.
Lord Frost urged the EU to make radical amendments to the protocol.
He stated: “If this is to work, we need to see substantial and significant change.
“It is going to need serious engagement with our proposals, and specifically with the three areas that we say need to change – movement of goods into Northern Ireland, the standards for goods within Northern Ireland, and the governance arrangements for regulating this.
“I want to be clear that any response which avoids serious engagement with those ideas, and aims at just dragging out the process, will in the end not work for us.”