Southeastern trains is to make 300 people redundant over the coming year.
The company blamed "reduced passenger journey growth" and the economic climate for the decision, which will see up to 90 staff axed by May.
A spokesman for the Rail Maritime and Transport (RMT) union described the cuts as "completely unjustified" and urged the government to intervene.
The company employs 4,000 people and operates services in Kent, South London and parts of East Sussex.
Staff affected by the job losses are to include a number of managers and administration workers, Southeastern said.
In a statement, the company said: "In line with many other companies in the UK at the moment, this step is being taken in order for us to remain a successful organisation.
"It's necessary to take these measures in a time of reduced passenger journey growth and a more challenging economic climate.
"It's expected we will lose 300 posts across the business as a whole over the next 12 months, starting with these 90 redundancies.
"It's envisaged that much of the remainder will go through ways such as natural turnover, not filling all vacancies when employees retire or leave."
The RMT urged the government to stop private transport firms "sacrificing" jobs and services to protect profits.
General secretary Bob Crow said: "This franchise has seen its passenger numbers grow by more than 6% and its passenger revenue grow by 13% in the last year."
He added: "They have been happy to cream it at the expense of massive subsidy, overcrowding and inflation-busting fare increases, but at the first sign of a downturn they want to make the rail workers who actually provide the service pay with their jobs.
"That is a disgrace, and in the current economic crisis the government should be telling Southeastern that it is not on."