The Parti Quebecois leader told a news conference the province could enact laws or regulations to make it difficult to implement a Canada-EU treaty if it believes there has been an encroachment on provincial jurisdiction.
"At one point, when it comes to certain principles with which we are unable to live or agreements that have an impact on our market that is unacceptable, well, I don't think we should give up," Marois said.
Such deals are just another reason why Quebec needs to be sovereign, the premier added.
Right now, the Canadian Constitution says only the federal government can sign trade deals with other countries.
Marois was speaking in London ahead of a speech she gave to the Canada-United Kingdom Chamber of Commerce.
Marois' tough talk reflects the PQ stand during the last provincial election that it would pick fights with Ottawa to get more powers. But Quebec's tone has been muted since Marois was voted in with a minority government.
The federal government has invited provincial input on free-trade negotiations with the European Union, which have been underway since 2008.
Federal International Trade Minister Ed Fast said at the World Economic Forum in Davos, Switzerland, last week that Ottawa wouldn't sign a deal unless it had obtained the consent of the provinces.
"The position we have taken is that we will sign a trade agreement only if it is clearly in the interests of Canada," Fast said. "For us, it's not the timing that matters most but the quality of the agreement."
Fast said there are still a lot of issues to work out but there is considerable goodwill.
Marois said Monday that indications for a deal are "quite positive."
Sticking points in the negotiations include opening European beef and pork markets and respecting pharmaceutical patents.
Marois says issues such as supply management, which protects Canadian producers of milk, eggs and poultry, are vital to Quebec.
In her speech to the chamber of commerce, the premier laid out her economic plan for Quebec.
She barely mentioned sovereignty in her address, putting more emphasis on plans to develop Quebec's north that have carried over from the previous Liberal government.
Her speech received polite applause from the collection of business leaders present.
Marois also attended an announcement by British special-effects firm Framestore, which says it will create 200 jobs in Montreal.
Quebec will give the firm an interest-free loan of $900,000 over five years and although Marois said it would get no tax credits, company CEO William Sargent said tax credits were one of the reasons Framestone decided to set up in Montreal. An experienced talent pool was also an attraction.
Framestone lists Hollywood heavyweights among its clients. Productions to be handled in Montreal include the remake of "RoboCop" from Columbia Pictures and MGM as well as "All You Need Is Kill" from Warner Bros. and starring Tom Cruise.
On Tuesday, Marois is to meet with her Scottish sovereigntist counterpart, Alex Salmond.
The Scots are due to vote on independence in the fall of 2014 but so far the option has the support of only about 30 per cent of the population.
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