Ed Miliband is to accuse David Cameron of putting efforts to hold the Tory party together ahead of the national interest, pointing to the referendum on Europe, which he says will result in "four years of uncertainty" for British businesses.
The Labour leader savaged Cameron in a speech to the Blairite progress group, insisting the PM is "weak" and "panicked" into holding the in/out vote on Europe in a bid to retain the support of his own MPs.
He insisted the UK should stay inside the European Union and instead press for changes to "make it work better for Britain".
Mr Miliband will say: "I know David Cameron is a man who likes to be known for relaxing - even chillaxing - but, on this occasion, it beggars belief.
"He's not lying on the sofa, relaxed. He's hiding behind the sofa, too scared to confront his own MPs.
"It's not chillaxing. It is weak and panicked. He's flailing around, directionless, unable to show the leadership the country needs because on this, as on so many issues, he has no answers to the challenges facing Britain in the future.
"And why is the Prime Minister in this position? Because he has consistently failed to lead his party on Europe and is, instead, being pushed around by his own backbenchers.
"That's the only reason he changed his mind in January on his previous position on an in/out referendum. It wasn't about the national interest, it was simply about his party interest.
"The great irony is that it hasn't even worked because his backbenchers keep coming back for more."
A series of Tory grandees including Lord Lawson and Michael Portillo have advocated withdrawal. Restive Tory backbenchers hope to force a Commons vote next week in protest at the Prime Minister's failure to table legislation to pave the way for the referendum.
Downing Street has said the Prime Minister is "relaxed" about the rebel amendment and hinted he could even allow Tory ministers to support it.
The Conservatives have been shaken by the rise in support for Nigel Farage's United Kingdom Independence Party, but Mr Miliband dismissed them as lacking solutions.
He said: "David Cameron may try to out-Farage Farage on Britain's membership of the European Union.
"But we will always stand up for the national interest.
"And our national interest lies in staying in the European Union and working for the changes that will make it work better for Britain.
"It is wrong now to commit to an in/out referendum and have four years of uncertainty and a 'closed for business' sign above our country.
"Let me be very clear: we will always make decisions on these issues in the national interest."
He will say Ukip "is a party of protest, not solutions to the deep problems the country faces" and "the Tories are fast turning from a party of government to a party of protest - against each other".
Mr Miliband told the Blairite Progress group his party needs to move on from the policies which swept New Labour to power, including a change in its approach to immigration.
"Almost two decades on, many of the truths that underpinned that project - truths that appeared to be so self-evident back then - have been challenged.
"Like the certainty of an old economic settlement that saw financial services as the main bedrock of our prosperity.
"Or the certainty that Britain's ever-increasing diversity would automatically benefit the whole country: that immigration would be acknowledged to work for all."
He said: "We are setting out a new economic plan fit for purpose in the post-crash world: a plan that acknowledges that there will be less money around and a plan that knows Britain's recovery will be made by the many, by the real wealth creators of this country.
"And on immigration, I bow to no-one in our commitment to a diverse, multi-ethnic Britain - it is one of things that makes our country great.
"But we have to make sure our diversity works for everyone, not just for a few at the top. And that requires government to play its role: in managing the pace of change, preventing exploitation at the workplace and ensuring we integrate as a country."
A Conservative Party spokesman said: "Ed Miliband is a weak leader who opposes giving the British people a say on our future in Europe in an in-out referendum, opposes our plan to fix the immigration system and opposes dealing with the deficit.
"All Ed Miliband does offer Britain is the same old Labour solution that got us into this mess in the first place - more spending, more borrowing and more debt."
In his speech to the Progress annual conference, Ed Miliband is ruled out an in-out referendum on the EU.
Commenting, Conservative Party Chairman Grant Shapps said: "David Cameron will give the British people their say on our future in Europe in an in-out referendum in the next parliament.
"But Ed Miliband has once again made clear he will never trust the British people to have their say - he opposes a referendum. He is too weak to stand up for the British people at home and too weak to stand up for our country's interests abroad."