David Cameron has pledged a "fightback" on HS2 after a barrage of criticism cast doubt on the flagship high-speed rail project's future.
The Prime Minister insisted there were "huge benefits" to the plans as the government published a new study arguing it would drive growth in the regions.
Analysis by KPMG suggests the economy may receive a £15 billion a year boost from the proposed link between London and cities in the Midlands and north of England.
Transport Secretary Patrick McLoughlin is stressing the importance of the increased capacity on the route, as well as the speed.
He has also dismissed fears that the £42.6bn budget could spiral out of control.
MPs on the Commons spending watchdog issued a scathing report on the scheme this week, warning the apparent benefits were dwindling as costs soared.
The case for the massive project was based on "fragile numbers, out-of-date data and assumptions which do not reflect real life" with no evidence that it would aid regional economies rather than sucking even more activity into London, according to the Public Accounts Committee report.
But Mr McLoughlin will point out the research by accountants KPMG, commissioned by HS2 Ltd, estimates the Birmingham area's economy will be boosted by between 2.1% and 4.2%, there will be a 0.8% to 1.7% benefit to Manchester, 1.6% for Leeds and 0.5% for Greater London.
He will say: "It addresses that vital question: will HS2 create jobs and growth in the North and Midlands, where they are needed most? The answer is absolutely clear. Yes.
"High Speed Two will make Liverpool stronger. Manchester stronger. Leeds stronger. Britain stronger. A £15bn annual boost to the economy. With the North and Midlands gaining at least double the benefit of the south."
The Transport Secretary's speech is part of a coordinated campaign by Mr Cameron to counter what he has called an "unholy alliance" of sceptics.
Prominent critics have included Labour's Alistair Darling, who first approved the project as chancellor, former business secretary Peter Mandelson, and the Institute of Directors.
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