Gordon Brown is to promise to keep Britain at the heart of Europe, insisting any "retreat to the sidelines" would jeopardise trade and jobs.
With the row over the controversial Lisbon Treaty set to dominate Westminster in the weeks ahead, the Prime Minister will stress that the European Union is vital to the British economy.
MPs will vote on the second reading of the Bill to ratify the treaty next Monday, ahead of at least a month of solid line-by-line debate.
With Eurosceptics preparing to pick at the details of the treaty and Tory leader David Cameron stepping up demands for a referendum, Mr Brown will condemn doubts about British membership.
In a speech to business leaders at a conference in Westminster, he will say: "What is clear is that at this time of global economic uncertainty, we should not be throwing into question our future membership of the EU - risking trade, business and jobs.
"Indeed, I strongly believe that rather than retreating to the sidelines we must remain fully engaged in Europe so we can push forward the reforms that are essential for Europe's, and Britain's, economic future."
He will go on to say that Europe is as important to Britain as ever, accounting for nearly 60% of UK trade and supporting 3.5 million jobs.
He will say that the enlargement of the EU, taking in 12 new members from the former Eastern bloc in recent years, is "perhaps Europe's greatest achievement" and made Britain more prosperous.
Having agreed the long-running debate in Europe about the EU's structures with the signing of the Lisbon Treaty last month, Mr Brown will say it is now time to address issues of competitiveness, jobs and growth.
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Having promised MPs plenty of time to go over the details of the Lisbon Treaty in Parliament, ministers have set aside four or five weeks for continuous debate during the ratification Bill's committee stage.
