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Sir Keir Starmer will call on the government to replace the furlough scheme and outlaw "firing and re-hiring" methods to avoid the "scarring effect" of "mass unemployment".
Almost 10 million workers have been furloughed since March but the scheme is set to end on 31 October.
The Labour leader will address the TUC, proposing targeted support for badly-hit sectors.
The government said it was already implementing a plan to protect jobs.
Employment Minister Mims Davies also hinted there could be a more targeted approach when Chancellor Rishi Sunak unveils his budget later in the year.
She said there would be "sectors that take longer to come back" from the pandemic, adding: "I don't think this government is afraid of supporting where we can [and we] have fiscal events where the chancellor can start to look at that."
Sir Keir's speech comes as the latest UK unemployment figures are released, showing the highest level for two years.
The unemployment rate grew to 4.1% in the three months to July - compared with 3.9% previously - with young people were particularly hard hit.
Speaking to the Trades Union Congress' annual conference, Sir Keir will make the case for replacing the job retention scheme - also known as the furlough scheme - which was introduced to support employers and staff during the coronavirus lockdown.
Under it, employees placed on leave due to virus restrictions have received 80% of their pay up to a maximum of £2,500 a month.
Since September, firms have had to start making a contribution to wages as part of the scheme winding down.
The government has been reluctant to extend the furlough scheme beyond October with Mr Johnson arguing that it would only keep people "in suspended animation".
A Treasury spokesman said: "We already have a national plan to not only protect jobs, but to create new ones - and we are implementing it right now.
"Thousands of young people will take their first steps into work through our £2bn Kickstart scheme this autumn and our up to £9bn Job Retention Bonus will help companies bring those on furlough back to work."
Skills and training
Sir Keir is expected to argue that "with a bit of imagination and acting in the national interest, a better approach is possible".
His alternative proposals include expanding part-time working and rewarding employers who give people hours rather than cut jobs; providing training and support for those who can't come back full-time, and targeting sectors most in need such as retail, aviation and those hit by local lockdowns.
"Imagine how powerful it would be if we could form a genuine national plan to protect jobs, create new ones and investing in skills and training," he is due to say.
"I'm making an open offer to the prime minister: Work with us to keep millions of people in work, work with the trade unions and work with businesses, do everything possible to protect jobs and to deliver for working people."
The Labour leader will also praise trade unions as "unsung heroes" saying: "Without you there would have been no furlough scheme, no life raft for seven million people."
Addressing the conference on Monday, TUC leader Frances O'Grady said: "If the government doesn't act, we face a tsunami of job losses."
During his speech, Sir Keir will also urge the government to outlaw "fire and re-hire" practices whereby companies sack employees but then hire them back on worst pay and conditions.
He is expected to say: "These tactics punish good employers, hit working people hard and harm our economy."
