Peladeau referred to Bombardier Inc.'s plans to cut 1,750 employees over the coming months because of declining demand for its business jets.
He also pointed to the recent sale of the Cirque du Soleil, which was acquired by American and Chinese investors and whose head office is in Montreal.
Peladeau, who became leader of the pro-independence party on Friday, asked Couillard if he has any plans to urgently intervene to better protect the province's head offices.
The premier's response was that Quebec's economic plan has begun to work and will continue to be effective.
"To attract and maintain head offices in Quebec, there's one important and essential ingredient — and that's economic, political and financial stability," Couillard replied.
"When we work to keep Quebec in the Canadian federation, when we work for sound and balanced public finances and a debt under control, we're acting in the way to attract and keep our head offices."
Earlier in the day, Couillard said Peladeau's plan for independence has nothing to do with reality and that the new PQ leader is living in a parallel world.
He said the sovereignty being proposed by the media baron is an imaginary solution to a problem that doesn't exist.
He told reporters his Liberal government will continue to focus on the economy.
"Talking to Quebecers about real issues and real solutions to those real issues — not imaginary situations, imaginary problems of course, not imaginary situations," he said.
"Quebecers are a happy prosperous people within Canada and they've thrived within Canada while still asserting their identity and who they are and who we are and that's again what we'll keep repeating."
Couillard also said Peladeau made it clear in his victory speech that Quebec sovereignty will be the major issue of the 2018 election campaign.
In his speech, Peladeau told supporters he had received the mandate from the party to make Quebec independent.
"The choice will be clear," Couillard said. "Monsieur Peladeau himself has made clear what the theme of the next election would be."
The premier, who was taking part in an investment announcement, added that Quebecers are more concerned with their quality of life, economic growth, jobs and the sound management of public finances.
Peladeau, who has steadfastly refused to sell his controlling stake in Quebecor Inc. (TSX:QBR.B), said he gave instructions on Friday to have a blind trust created where his shares will be parked.
He said he is now waiting for federal authorities to take action, stressing he is not responsible for any delays.
"As you know this is about telecommunications and broadcasting, so therefore all those licences need to be transferred and we need the approval of the appropriate federal authorities do so," Peladeau said.
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