It's a disruptive move that shifts the landscape of federal politics in an election season. Duceppe, the former leader of the sovereigntist party, lost his own seat seat in the 2011 election, when his party suffered a massive reversal at the hands of the New Democrats in Quebec. He then promptly resigned as party leader.
A lot has changed, though, since his last run in federal politics.
Here are some things Duceppe will have to take stock of now that he's back in the ring.
A sovereignty movement that's a shadow of its former self
In 2011, 43 BQ MPs were catapulted from their seats in the House of Commons.
In 2014, a projected majority for the Parti Québécois in the provincial election morphed into a 24-seat loss and the exit of Pauline Marois as leader after the party announced the candidacy of media mogul Pierre Karl Peladeau (and his raised fist for secession!).
Combined, the two events were a huge setback for the sovereignty movement in Canada.
If a poll was conducted today deciding on Quebec independence from Canada, about a third of Quebecers would say yes to independence, according to pollster Christian Bourque. However, that doesn't necessarily translate into votes for sovereigntist parties, as recent elections have shown.
"So that difficulty that they are having, I think, speaks a lot about what we should expect in next election here in the province of Quebec," Bourque said in an interview with CBC News.
Quebec is undergoing a generational shift
Bourque also suggested Duceppe and the Bloc Québécois represent an older political guard that doesn't resonates as much with Quebec voters.
"In 2011, symbolically, Quebecers wanted to turn the page on one way of doing federal/provincial politics in Canada — this sort of old 'us against them,' the English against the French," said Bourque, who's also executive vice-president of Leger Marketing.
Meanwhile, a new generation of Quebec voters is divided mostly on the left and right, as well as on energy policies, natural resources, education and social programs.
To young voters who care about a wide range of social and political issues, a platform based on independence will sound fairly shallow, Bouque said.
Duceppe's foray back into politics shows the BQ is trying to flip back to an old page in the playbook.
"It's like the Rolling Stones announcing yet another farewell tour. Some people will get excited, but a lot of people may just say, 'Yeah, you know what? It's over.'"
It won't be an easy incumbency this time around
With their numbers decimated after 2011, the BQ will be in an offensive position in the upcoming election — from a tactical point-of-view, much more difficult than heading into the race as the incumbent.
"Since they always made this about 'us versus them,' I think the Bloc will face a problem with having many enemies. In Montreal, it's (Liberal Leader) Justin Trudeau. In the regions, it'll be (NDP Leader) Tom Mulcair," said Bourque.
They'll need to fire on all targets at once, which will require new strategies to win over Quebec voters who see the NDP or Liberals as alternatives to the Conservatives.
"I don't know if they have the right cast for that," he said.
The loss of the per-vote subsidy hurts
The BQ may be the party most vulnerable, financially, now that the per-vote subsidy is no longer available.
The publicly-financed subsidy, which ended on April 1, saw Elections Canada give political parties payments proportionate to how many votes they receive in the previous general election. It was originally $2 per vote and ultimately diminished to about $0.13 per vote by the end.
The BQ benefited most from the subsidy and right now they're lacking money, noted Martin Patriquin, Maclean's Magazine Quebec bureau chief, in an interview on CBC News Network. The party received $3,977,147 in total subsidies from the 2011 election results.
It hurts because the BQ operates under an older, grassroots style of politics that is also quite expensive, said Bourque.
"So we might actually get an idea of how well the Bloc Québécois may do in October based on how quick and how much money they can raise from voters in the next few months," he said.