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The Hammers are 18th in the table with one match remaining, and will be as good as relegated to the Championship if Tottenham - two points above them with a game in hand and a much better goal difference - draw with Chelsea on Tuesday.
Under the 99-year lease agreement, West Ham would pay the Greater London Authority about half their current annual rent of £4.4m if they are relegated.
London taxpayers, who currently contribute to stadium operating costs such as stewarding, will have to make up the funding gap.
"If West Ham are relegated, we, the taxpayers, we City Hall, could lose up to £2.5m a year," said Mayor of London Sadiq Khan.
"So what I say to Londoners who don't support Spurs is you should probably be cheering on West Ham, because the taxpayer will lose out if West Ham go down."
Khan blamed predecessor Boris Johnson for agreeing "the worst deal imaginable" in 2012.
Commercial revenues from London Stadium are expected to fall if West Ham play in the Championship, while stewarding costs over 23 home games would be greater than 19 Premier League home matches.

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