Up to 200 posts are to be cut at the biggest hospital in the South West.
The hospital said it had a £22m overspend
Managers at Derriford Hospital in Plymouth said the move was because of a £22m budget shortfall.
They said they hoped to keep redundancies to a minimum and look for savings through natural wastage and freezing non-essential vacant posts.
A union spokesman said the news on Monday was not surprising, but his concern was for staff morale and how it would affect patient care.
Kevin Norman, of the GMB Union, told BBC News: "The major concern is how we got to a figure of £22m when they've known about it for some considerable time.
"It's an enormous figure which should have been dealt with before."
The hospital said it hoped to minimise the number of redundancies it would have to make and that it would work with unions throughout the process.
Paul Roberts, the hospital's chief executive, said the Plymouth Hospital NHS Trust had received greater investment in recent years, allowing it to double the number of consultants and recruit an additional 600 nurses and midwives.
"But the levels of new investment are not enough to fund everything we need to do and so we have to look at the way we work and part of that process is continuing to look at the way we employ staff", Mr Roberts said.
"We have to balance our budget and make sure we are as efficient as possible and the money we do have available is concentrated on direct patient care."
Earlier this month it was announced that 300 jobs were to be cut at the Royal Cornwall Hospital Trust in Truro in a bid to tackle an £8.1m deficit.
The Cornwall trust said some operations would also be cancelled with wards and operating theatres closed as part of the cost-cutting plans.