Preserving post-Brexit trading rules for goods moving between Great Britain and Northern Ireland is "the only way" to avoid a hard border, warns the EU.
European Commission vice president Maros Sefcovic has written to the UK's Michael Gove, saying "teething problems" needed to be resolved.
It comes after Mr Gove called for an urgent "reset" of the arrangements that came into force on 1 January.
Mr Sefcovic and Mr Gove will discuss the issues in London on Thursday.
The so-called Northern Ireland Protocol was designed to ensure an open border between Northern Ireland and the Irish Republic after Brexit.
Northern Ireland remained in the single market for goods, but the rest of the UK did not - meaning some checks for goods travelling between Great Britain and Northern Ireland were introduced.
Tensions have been high in recent weeks at ports in Northern Ireland, with disruption to some food supplies and online deliveries due to the new checks required.
Unionists want the protocol to be scrapped because they say it damages trade and threatens Northern Ireland's place in the UK union.
But the EU has stood by this part of the post-Brexit trade agreement, finalised in December and coming into force on New Year's Day.
Mr Gove told MPs last week that, while the UK did not want to "ditch" it, it "reserved the right" to do what it must to protect Northern Ireland.
In his letter, Mr Sefcovic said he welcomed "the shared commitment" between the UK and the EU to work together to solve the difficulties.
But he stressed that Brexit had caused problems, adding: "The UK's withdrawal from the Union, its single market and customs union presents unique and significant challenges for the island of Ireland."
He said the UK and the EU had a shared objective to "work tirelessly in order to make the protocol work" because it was "the only way" to protect the Good Friday Agreement, and to avoid a hard border on the island of Ireland.
Mr Sefcovic also said the EU and the UK had a "common responsibility to diffuse tensions and to ensure the safety of staff on the ground".
Checks at some ports were temporarily suspended at the beginning of February over "sinister" threats made to some border staff who were carrying out checks on goods.
The Commission vice-president said it had come to his attention that border control posts were not yet fully operational and a number of consignments were entering Northern Ireland without being properly declared and without proper certificates.
But he said he hoped these were "teething problems" for which "swift solutions" could be found.
Northern Ireland's First Minister, Arlene Foster, accused Mr Sefcovic of "putting his head in the sand and his fingers in his ears" over concerns her party - the DUP - had raised.
She told ITV's Peston that the call to strengthen the protocol, despite the problems raised by unionists, was an "incredible state of affairs".
Ms Foster said the protocol was not only creating problems for businesses, but consumers too having problems with parcel deliveries, adding: "You can't even get a pot plant from Great Britain."