"I'm always open, but no blank cheque and certainly not with Stephen Harper," Duceppe said in an interview airing Sunday on CBC News Network's Power & Politics.
"When he had a majority [in 2011], we then saw the real Stephen Harper and I don't see any possibility of supporting any kind of coalition with him."
Duceppe said the Conservatives won in the last election because "the Liberals and NDP divided the vote" in Canada, but not in Quebec.
"Harper only has five members elected in Quebec," he pointed out. "The question in Quebec is, people want to beat Harper, and what we're telling people is that we always won over Harper."
NDP poses real risk to Bloc
But the Conservative Party leader may not be Duceppe's main challenger to fear in the upcoming election.
Despite saying that "for years, the NDP was not a real opponent," Duceppe admitted that the political scene has changed, and that now NDP Leader Tom Mulcair is the man to beat.
"In a certain sense, we are in the place the NDP was in the beginning of the last campaign, and they are where we were. It changed during the  campaign and we have the firm intention to change that also," he said.
In 2011, the NDP's "Orange Crush" resulted in a near sweep of the province, winning 58 of Quebec's 75 seats and reducing the Bloc to a meagre four from their previous 47. Duceppe lost his own seat to NDP candidate Hélène Laverdière and resigned after having led his party through six elections.
Now, his comeback as Bloc leader is focused firmly on preventing a similar orange wave from cresting once more.
"I still have six weeks to tell [Quebecers] that the real Thomas or Tom is, when you look at it, a Liberal supporting a Liberal and we're against those policies in Quebec," he said of Mulcair.
Duceppe warned that if elected, the NDP would not defend Quebec's interests in Ottawa.
"They're saying something in Canada and another thing in Quebec," he said. "We have Tom in Canada, and Thomas in Quebec. So two persons in the same body."
When asked for examples, Duceppe pointed to the NDP's pipeline policy on Energy East. Mulcair has said he would allow the pipeline if it passed rigorous environmental study.
"Almost everybody is against the pipeline and they just don't understand why the NDP is supporting it," Duceppe said of the project, which is controversial in Quebec. "We all know they don't want to lose votes in the West, in New Brunswick. We can come with a lot of examples of the NDP supporting things Quebecers are against."
Austerity the worst strategy, Duceppe says
Duceppe also has concerns over the future of Quebec sovereignty under an NDP government.
"Our strategic vote for sovereignty in Quebec is certainly not to vote for someone who said themselves he was one of the most important opponents to Quebec sovereignty," he said.
"So why would you give the ball to someone playing for the other team?"
There is one issue where there is consensus between the Bloc and the NDP, Duceppe said.
"On certain policies, like Thomas Mulcair supporting the right for Quebecers to decide their own future in a referendum at 50 per cent plus one, Trudeau is against," he said.
"So on that policy, I prefer Mulcair, of course."
But Duceppe hinted he favours the Liberal approach to go into deficit spending on infrastructure for at least the next three years.
"The NDP is proposing the same thing as Stephen Harper — austerity. It's the worst strategy when you're facing an economic crisis," he said.
"We're not proposing a huge deficit, but proposing austerity is the worst proposal," he said, adding that his position against austerity isn't an endorsement of the Liberals' deficit spending either.
"Before commending the NDP, Liberal or Stephen Harper's plans, I want to see the whole plan," he said. "Where are they taking money? From the Employment Insurance Fund? I want to see all of that before committing to a plan."
Bloc ready for phase 2 of campaign
With Labour Day marking the unofficial second phase of the 11-week campaign, Duceppe said his party is ready to ramp up campaigning activities in the final six weeks before the election.
"It is already serious but I think it will look different than the first phase of the campaign. The plan was to go around each region of Quebec — there are only two regions I haven't gone to yet," said Duceppe, who added the Bloc will have an "important meeting" on Sept. 7 "with the posters and slogan and platform of the campaign."
Also on HuffPost: