The gambling giant behind Ladbrokes and Coral plans to cut 400 jobs, while warning Andy Burnham that a tax raid on the sector could lead to more than 1,000 betting-shop closures.
Entain is consulting on removing around 400 customer-service roles, mainly in the UK, out of a total of around 2,000.
The global gambling company had already cut 500 jobs this year before the latest round of redundancies.
It comes as Mr Burnham is weighing up launching a tax raid on slot machines, targeting betting shops and arcades for adults.
However, Stella David, the chief executive of Entain, has warned the Prime Minister that hundreds of betting shops and thousands of jobs would be at risk from further tax rises.
Ms David said in an open letter to Mr Burnham last week: "You have spoken about the Makerfield Test – the principle that national policy should deliver for places and people that have too often been overlooked by Westminster.
"A substantial increase in machine games duty (MGD) would bear directly on many of the people and places the Makerfield Test is intended to support."
Ms David warned that doubling the rate of the levy would land Entain with an additional £100m annual bill.
She added: "Independent modelling from EY shows the potential consequences across the sector, indicating that a 40pc MGD rate could lead to up to 1,470 betting shop closures and 15,900 job losses, and ultimately result in a net loss to the Exchequer of around £120m."
She warned that job cuts from higher taxes would disproportionately hit young people and women working part-time.
However, it is understood that Mr Burnham and John Healey, his Chancellor, believe slot machine venues that are open 24 hours a day are wrecking lives and high streets.
Labour's gamble
Gordon Brown, the former Labour prime minister, is among those calling for greater taxes on gambling.
But industry leaders have warned that any further attempt to lump it with tax rises will drive gambling into unregulated markets that do more harm.
Rachel Reeves, the former chancellor, raised taxes on online gambling from April 1 this year , with a further levy to take effect a year later.
The changes are forecast to raise an extra £1.2bn from the sector by the start of the next decade.
Ms David warned in her letter: "A further doubling of machine games duty would therefore add another significant cost to businesses already struggling to absorb major tax increases, stacking the odds against labour-intensive high-street operators and making it harder to sustain shops, jobs and investment in local communities."
It comes as inflation-busting minimum wage rises and a £26bn National Insurance tax raid on employers under the Government have been blamed for an economy-wide slowdown in hiring.
Some 145,000 fewer people were employed on payroll in August compared with a year earlier, new figures from the Office for National Statistics show.
The biggest job losses have occurred in retail.
