Treasury analysis claims 285,000 jobs in the sector are linked to European Union financial services exports.
And the chancellor said this evening that leaving the single market “would be catastrophic for jobs and incomes”.
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Osborne also encouraged all those in the business community “who know what's at stake [to] speak up”.
Treasury research suggests around 100,000 financial services jobs are directly linked to EU exports and 185,000 more are reliant on indirect demand that is created by that business.
Speaking at an event today, Osborne said: "Tens of thousands of jobs in financial services and connected industries would be at risk if Britain votes to leave the EU on June 23."
He was expected to say: "The financial sector’s importance to the UK economy cannot be overestimated. It’s worth more than seven per cent of our total GDP and exports around £69bn worth of services in total every year, of which over £20bn goes to the EU.
"It is a key part of the UK economy and has gone from strength to strength with Britain as part of the EU. A vote to leave the EU would put all this at risk."
Vote Leave hit back at the claims, with a spokesman saying: "A decade ago we were told the City would be wiped out if we didn't join the euro, now they are saying the same about the referendum.
"The same banks that crashed the global economy are the institutions now plowing money into the remain campaign.
"If we Vote Leave we can regulate the wide-boys while allowing financial exports to grow across the world."