The 48-hour strike is the second since January against the job cuts, which already total 17,700 in the past 18 months.
Up to 90,000 people in more than 1,000 offices run by the Department for Work and Pensions could join the protest, and there are fears a civil-service wide strike could follow as a result of government plans to further cut public spending.
The general secretary of the Public and Commercial Services Union (PCS), Mark Serwotka, said that jobs and benefits services were deteriorating as a result of the job cuts.
"Our members are left having to strike to defend the services they care about," he said. "Senior management can no longer continue to plough on regardless. Rather than continually being in denial saying everything is fine, the department needs to halt the job cuts programme."
The job cuts come as a result of efficiency savings announced in the 2004 budget, and aimed at reducing the Department for Work and Pensions' total budget 5% by 2008.
The DWP is moving much of its service delivery away from shopfront centres and towards a string of call centres, but problems with the system have been heavily criticised in Westminster.
In March, the House of Commons work and pensions select committee castigated a "truly appalling" and "catastrophic failure" in the Jobcentre Plus service last summer.
The select committee report said that the speed of implementation had left managers struggling to keep up with the number of IT, telecoms, financial and organisational changes being imposed by the government.
It also criticised Jobcentre closures, which have left people in rural and some urban areas having to travel further to get help.
A National Audit Office report in March found that 20m calls to the disability and carers' service call centre had gone missing, accounting for around 80% of calls to the service.
A PCS spokesman said the union wanted a guarantee of no compulsory redundancies and a chance to sit down with the DWP to discuss a suitable level of job cuts.
"The days are gone when you can just walk into a Jobcentre and have your situation dealt with," he said.
"Now you phone a call centre, they take your details, arrange a time to call you back, someone calls you back and arranges a time to make an appointment, and finally you go into a call centre. There are delays of up to six weeks in this," he said.
The DWP said there had been no compulsory job cuts and that call centre services had improved considerably since the critical select committee report, with over 95% of calls answered and more than 120,000 new cases handled each week.
"If we are going to meet our commitment to deliver the highest quality of services it is vital we push ahead with our modernisation programme. It is disappointing that the PCS union remains opposed to much of those changes," a spokesman said.
