In a wide ranging interview with regional journalists today, Mr Hammond spelt out the seriousness of leaving the EU as a permanent decision that could not be reversed.
He claims it would be better for people in Yorkshire to stay, and that it's always possible to hold another referendum in '20...30 years' time if the EU is heading in a direction the British people don't like.
As the Prime Minister kick-starts his fight for Britain to remain within a reformed EU, Mr Hammond said he expects some Eurosceptics to campaign aggressively in the run up to the June 23 election.
He said: “There are people with very firm views on this. They will express their views very strongly, and in some cases aggressively but they are never usually the majority.”
Despite almost 4m people voting for anti-EU party UKIP at the General Election, Mr Hammond is confident they won’t have a significant impact on the referendum’s outcome.
He said: “I seem to remember at the last General Election, we were told similar things about Eurosceptic voters - that we would be drowned in a sea of UKIP.
“It didn’t happen because they make a lot of noise, but they are not by any means a majority. In fact they are a tiny minority.”
He said the vast majority of British people will be quiet on the subject, making their decision privately and pragmatically.
He said: “I’m pretty confident they will focus on whether Britain will be stronger, safer and better off inside the EU, or outside the EU.”
The Government has announced Britain’s first in/out referendum on membership of the EU in 40 years after Mr Cameron secured a package of reforms at the EU Council on Friday night.
The Prime Minister wants to use the deal he’s brokered for Britain to have a reformed relationship with Brussels as the basis of his campaign to remain in the union.
No 'sweet deals'
He warned Brexit would lead to Britain having to strike 27 separate trade deals with EU states to access the single market, and fellow members would not cut the country any ‘sweet deals’.
So wounded by a vote to leave, he claimed Britain would pay a price when it went back to negotiate access with its European neighbours.
He said: “If we vote to leave the EU we will have to negotiate with the remaining 27 what kind of terms of access they will be prepared to give us to the single market and what price they will extract from us for that access.
"I don't believe the other 27 countries of the EU will be driven in that negotiation by a desire to see Britain as successful and as prosperous as possible
"Far from it. Many of them will be deeply hurt, injured that we have left the EU.
"They will believe that our action has threatened the EU and possibly threatens their own political arguments in their own home countries where they too will have Eurosceptics.
"I don’t think they will be looking to do us any favours. They will be looking to drive a very hard bargain for us for whatever access we are able to secure to the single market.”
Cutting all ties with the EU would be final he warned, and said all voters must consider the 'permanence of irreversibility'.
He said: "Leaving the EU would be irreversible and if we find life is colder and more inhospitable than some people had imagined it will be too late then."
He's confident that Britain will continue to shape the EU in its best interests in the coming years, but added 'nothing says that we can't ask ourselves this question again in the future in 20, 30 years time if we find Europe is not heading in the direction that we want it to.'
Mr Hammond said he respects the views of well-known Eurosceptic Conservative MPs, David Davis (Haltemprice and Howden) and Philip Davies (Shipley), but 'what matters is what's in the interest of the people of Yorkshire'.
He said: "Yorkshire of course is an important rural region but it's also an important manufacturing economy as well and many Yorkshire manufacturers, small and medium businesses, as well as larger ones, will look to the EU as a very important market for their goods and products."
He said the EU's Common Agricultural Policy had also delivered 'prosperity' to farmers and if Britain voted to leave the government would have to start a new regime for the sector 'from scratch'.
He said: "Most people will make their decision by balancing the arguments in favour and against."