Deputy First Minister Martin McGuinness has said the implications of a UK withdrawal from the European Union would be "absolutely enormous" for Northern Ireland.
However, Democratic Unionist Party MP Nigel Dodds said Northern Ireland would benefit from a UK exit from the EU.
A referendum will be held on whether to remain in the EU on Thursday 23 June.
Prime Minister David Cameron will go to parliament later to present his argument for staying.
He will outline the details of the deal he agreed with other European leaders last week.
Speaking to the BBC, Mr McGuinness questioned how a withdrawal would affect agreements made during the peace process.
The Sinn Féin minister said: "Anybody that has examined our relationship in the north with the EU over the course of many years, can't fail to recognise enormous benefits there have been for the community and voluntary sector, farmers and business community.
"I believe that right across the community - unionist and the broad nationalist/republican community - the majority of people place great value on our membership of the European Union and they want that to continue.
"The other implication that we have to consider is given the fact that there appears to be an intention in Europe to tighten borders.
"How, for example, will that have an effect on people who travel from Belfast to Dublin, from Derry to Buncrana, from Newry to Dundalk?"
The deputy first minister also called on Northern Ireland's Secretary of State Theresa Villiers to resign following her public support for a UK exit from the European Union.
"Isn't it odd that Theresa Villiers should now be advocating withdrawal from the EU when clearly the benefits for the north are very, very obvious," he said.
A spokesman for Ms Villiers described calls for her to resign as secretary of state because she had chosen to campaign for the UK's withdrawal from the EU as "ludicrous" and "ridiculous".
The spokesperson added that Ms Villiers remained 100% committed to doing her job as secretary of state.
Mr Dodds said Mr Cameron's deal had not "delivered fundamental change".
He said a UK exit from the EU would mean a "lot more money available to the UK and Northern Ireland. We currently transfer £55m every day to Europe".
"We will be better off, we will have better control over our laws and borders. We will make the decisions," he said.
"The amount of money that goes to farming has steadily decreased from 73% in 1985 to only 40% now. EU focus is moving away from food production so the idea that somehow there's a great guarantee for anyone in terms of the current status quo in Europe is wrong.
"If you vote to stay in, it's the risky option because Europe will override Britain and Northern Ireland's best interests over and over again.
"For every £1 we get back [from the EU], we pay in £1.58."
The SDLP and the Alliance Party are to campaign for the UK to remain in the EU.
The Ulster Unionist party has said their ruling executive will meet next week to decide its position on the issue.