Up to 450 jobs could be axed at Norfolk and Norwich University Hospital this year as part of plans to reduce a £14.8m budget deficit.
The Norfolk hospital project was one of the first PFI schemes
The trust board said a lower than expected national pay deal for NHS staff had reduced its predicted £22m shortfall for 2006/7 by more than £7m.
Managers said savings could be made by cutting pay and costs or reducing staff numbers currently standing at 5,600.
The Royal College of Nursing (RCN) said unions were talking with management.
The RCN's Hazel Bush said nurses at the hospital were "extremely worried".
She added: "We haven't heard as yet where these redundancies are going to be. So until that point I would urge them not to worry until we have exact figures.
"But the unions are working closely with the management and they are trying their best to make these redundancies natural wastage."
The trust's chairman David Prior said he also hoped many of the jobs would be lost through natural wastage.
He said: "No-one in this hospital sits on their backsides doing nothing. We want to keep as many staff as we possibly can."
Lobby health secretary
In a statement the trust said: "We believe that if we took no other action to reduce pay and other costs we would need to lose approximately 450 posts during this year.
"To reduce this number we need to significantly reduce the pay bill.
"There are a number of ways of doing this including better management of sickness and greater flexibility around rosters, shift patterns and out of hours working for all staff groups."
On 10 May Norfolk MPs plan to meet Health Secretary Patricia Hewitt to lobby for more support for the hospital.