In a damning report, they warn that ministers have failed to make a "convincing" case for the £50 billion HS2 project.
It follows warnings that costs could spiral out of control, with some estimating that the final tally could be as high as £80bn.
A number of former Labour ministers, including Alistair Darling, have expressed concerns about the project in recent weeks.
And last week, Coalition ministers signalled a change in the rationale behind the plan, suggesting it was to ease congestion rather than shorten journey times.
Today, the Commons Public Accounts Committee warns that the Department of Transport has failed to present a "convincing strategic case" for the rail link.
The project is based on "fragile numbers, out-of-date data and assumptions", it says - including that business travellers would not work on trains on laptops. The report also warns there is no evidence the line will aid regional economies and not "suck" more activity into London. It also warns a target of securing legislation by 2015 risks a repeat of errors such as those seen on the West Coast mainline.
Tory Transport Secretary Patrick McLoughlin insisted that without HS2, key routes would be "overwhelmed" by rising passenger numbers.
He said: "It will free up vital space on our railways for passengers and freight, generate hundreds of thousands of jobs and deliver better connections between our towns and cities."