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Britain leaving the European Union could cause serious disruption for the country as it tries to reorder its trading relationships, she told BBC television.
"It could very well mean that there would be more pressure on businesses in Britain, if not to leave completely, at least (to) also have sites and employment elsewhere in Europe.
"The disruption for Britain could be quite serious," the former US secretary of state said.
As Britain's divorce discussions with the EU stumble on, London now admits it is actively preparing to leave in March 2019 without agreeing a trade deal, which would mean operating on World Trade Organisation tariff rules.
Clinton suggested that commercial ties with the EU could not be replaced by a new trading relationship with the United States under Trump.
"You're making a trade deal with someone who says he doesn't believe in trade," she said.
EU negotiator Michel Barnier said Thursday that Britain and the bloc are stuck in a "disturbing deadlock" over London's financial settlement, although a breakthrough remains possible over the next two months.