Independence would rid Wales of the Conservatives "forever", Plaid Cymru leader Adam Price has told his party's conference.
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He said the next Tory prime minister should be "the last Tory ever to rule over Wales against Wales' wishes".
He also called for Labour to stay away from Plaid heartland seats at the next election.
He also referenced a "difficult summer", alluding to Jonathan Edwards, an ex-Plaid MP who assaulted his wife.
Plaid Cymru also announced a plan to cut energy prices, freeze private rents and make public transport cheaper.
Mr Price called it a "socially just and instantly deliverable" way to help with the cost-of-living crisis.
Following Liz Truss's resignation as prime minister, Mr Price said Conservatives have "no mandate, no credibility and no legitimacy left".
Plaid Cymru has three MPs at Westminster and 13 of the 60 seats in the Welsh Parliament, where it is in a co-operation agreement with Labour.
