The head of Nissan has warned the car maker would "reconsider" its future in the UK if it left the European Union.
Speaking at the launch of Nissan's new Qashqai model, he said: "If anything has to change we (would) need to reconsider our strategy and our investments for the future."
But he added that he considered such an exit unlikely.
The new Qashqai will be built at Nissan's Sunderland site, which employs 6,500 workers.
Prime Minister David Cameron has promised a vote on EU membership in 2017 if the Conservatives win the next general election in 2015.
Writing in The Times, he warned that the EU was a "job destroyer" and that leaving would not be an "unattractive option".
Asked about the prospect of Britain leaving the EU, Mr Ghosn told the BBC: "Obviously it's going to be a major factor happening and we are going to need to consider what does it mean for us for the future.
"I'm not worried about Sunderland. Sunderland is a very competitive plant, it's a very productive plant and it's a European plant based in the UK.
"If anything has to change, we need to reconsider our strategy and our investments for the future."
John Mills, co-chairman of the Business for Britain group, which is seeking reform of the UK's EU membership, told BBC Radio 4's Today programme: "If Britain were to leave the EU - and that's not what Business for Britain is advocating - I think that Nissan and any other car company would have to take a view as to what the prospects were, particularly if we continue to have free trade with Europe, which is very likely to happen.
"What we are saying is that if there's renegotiation then a much larger proportion of British business would want to stay in. I think Mr Ghosn would be wise to support what we say, which is to push for these negotiations to be successfully accomplished."
Fiona Hall, Liberal Democrat MEP for the North East, said: " This is a stark warning about the catastrophic damage the North East economy would suffer if we were to pull out, and it is one we cannot afford to ignore.
"Nissan is not just 6,000 jobs on Wearside, it is many thousands more across the region.
"Their importance to the North East can hardly be overstated.
"Workers and their families will rightly be asking why Ukip and the Conservatives are playing fast and loose with their jobs by talking up an exit instead of focusing on doing more to encourage the recovery.
"Fortunately I think Mr Ghosn is right when he says an exit is unlikely, because the business case for staying in is overwhelming.
"But the uncertainty that has been created by politicians putting their self-interest ahead of the region's economic well-being is already jeopardising investment."
Shadow business secretary Chuka Umunna said in a tweet: "The comments of Nissan's CEO underline the absurdity of Tories promising more investment and exports while seeking to take us out of the EU."
But Ukip general secretary and European election candidate Jonathan Arnott said: "Mr Ghosn's main comment is that if Britain left the EU, that would mean the situation would have changed. I quite agree. Britain would then be a more competitive market place as we could negotiate our own terms of international trade.
"The scaremongering that is once again going on is absurd. EU countries export 801,000 more cars to the UK than they import from us - we are a vitally important market place for them and that simply would not change.
"I am sure Nissan's investment into the UK will continue when Britain leaves the EU. After all in 1999 some in Nissan warned that if Britain didn't join the euro that could stifle investment. Instead they opened a new plant in Sunderland in 2012."