Guardian staff have been warned that 250 staff will have to go as the title's publisher seeks to cut £54m a year from its annual running costs.
A further 60 positions are expected to go by not filling vacant positions.
The job cuts will include editorial and compulsory redundancies have not been ruled out. The Guardian's heavily unionised workforce has previously indicated that compulsory journalist cutbacks would be a trigger for strike action.
Operating losses will total £58.6m for the year to the end of March and some 100 editorial jobs are to go out of 725 employed by the title. As of last year, GNM had 968 "core editorial staff" – a figure which is understood to include a number of freelances and casuals.
The company's investment savings have declined by more than £100m to £735m over the last year.
Editor Katherine Viner and chief executive David Pemsel announced the proposed cutbacks in an email to staff. They are part of a three-year plan to reach break even at an operating level by 2018/2019.
The letter states: "Our plan of action has one goal: to secure the journalistic integrity and financial independence of the Guardian in perpetuity.
"In light of the volatile media environment, there is an urgent need for radical action. In recent weeks, therefore, budget holders, the strategic cost group and the GNM Executive Committee have examined both our fixed and our operating costs, working up a series of proposals for year one that will allow us to reduce costs and set the stage for growth.
"Given that over half our current costs are people, we propose to reduce our UK headcount by around 250 people. While protecting journalism remains our priority, we anticipate the impact will be spread across all departments, including editorial.
"We hope to achieve the target reductions through voluntary redundancy. If we do not achieve the reductions we are targeting by voluntary means, we will consider whether compulsory redundancies are necessary."
Proposed changes including reducing the amount of space The Guardian occupies at Kings Place.
GMG has also confirmed that is scrapping the well-advanced project to create a 30,000 square feet events space and cultural venue in the Midlands Goods Shed.