The Queensland senator announced on Monday he will seek preselection for the electorate of Capricornia, days after sitting coalition MP Michelle Landry announced she would vacate the seat she has held since 2013.
"Someone's got to step up, and I'm the next person up here in central Queensland, so I'll put it on the line," he told reporters in Rockhampton.
"Who knows, I might not be successful, my political career may die, but I'm not going to die wondering."
Senator Canavan is second on the opposition's Queensland Senate ticket behind Liberal James McGrath, meaning a strong showing from One Nation in 2028 could boot him from his upper house seat.
One Nation placed third on primary votes in Capricornia at the 2025 federal election, snagging 15 per cent of first preferences behind the LNP and Labor and registering about a one per cent swing in their favour.
The coalition holds the seat by a 5.8 per cent margin.
Senator Hanson on Monday said she was previously unaware of the Nationals leader's planned lower house tilt and said she would not contest the seat herself.
There was rife speculation One Nation would run its national director James Ashby against the Nationals leader in Capricornia, but Mr Ashby ruled that possibility out on Monday.
"I'll play a role in the campaign here in Capricornia, but my position as national director is one that I take seriously, therefore I won't be nominating at preselection," he said in a statement.
"Capricornia is a seat One Nation can win, so I intend to throw the resources and people behind a strong campaign."
Senator Canavan had downplayed speculation he would move chambers but said he would do what it takes to keep the coalition's strong foothold in the region despite the prospect of a One Nation wipeout.
Opposition Leader Angus Taylor praised his junior coalition partner for "putting it all on the line" by attempting the move to the lower house.
"I was very pleased to see Matt is throwing his hat in the ring," he said on Monday.
"We're all putting it all on the line because we have to, because we need our country back."
Senator Canavan's fate is now in the hands of rank-and-file coalition members who will decide whether he is preselected.
If successful, he will have to resign his Senate seat before getting on the ballot in Capricornia.
"I hope to get that endorsement of the LNP members, we're a grassroots party - it's up to them," the Nationals leader said.
"And if I do get that honour, I'll be fighting like hell."
Senator Hanson has staged a comeback in The Australian's nationwide Newspoll released on Monday, with her net approval jumping eight points to minus one per cent in the space of a month.
The party also announced it would open a branch in Yeppoon, where Senator Canavan lives, late last year to "help shape the future of One Nation in the region", its website reads.
Nationals Senate leader Bridget McKenzie said One Nation should not be contesting coalition-held seats if it was serious about taking the fight to Labor.
"Matt's a great leader and is making a great impact for the coalition more broadly across the country," she told Nine's Today on Monday.
"If One Nation is really serious about firing the liar, then they need to start running in Labor Party seats instead of running against someone like Matt Canavan."
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