Ruth Davidson will tell her party conference that Scotland has "passed peak Nat" - claiming support for the SNP is on the decline.
The Scottish Conservatives virtual spring conference is due to start on Saturday afternoon, running through to Monday.
Davidson, who leads the party at Holyrood, is due to give a speech on Saturday afternoon.
She is not running for re-election as an MSP and is expected to enter the House of Lords when the current session of the Scottish Parliament ends.
Davidson will say: "Over the last few weeks, something in Scotland has changed.
"We've passed peak Nat and, more and more, Scotland is saying, 'enough'.
"An SNP majority government - once seen as a nailed-on near-certainty, and for so long the outcome almost universally forecast amongst the pundits - now looks much less sure.
"It's vital that majority is stopped because it's the only way to be certain that Scotland isn't dragged back into another independence referendum when we all need to be focusing on building a recovery from the pandemic."
Her speech will also say: "At the last election in 2016 the SNP fell just two seats short of an overall majority.
"That derailed their drive for another independence referendum five years ago.
"And it was achieved because people right across Scotland who wanted to stop the SNP gave their party votes to the Scottish Conservatives.
"We did it together, and we can do it again."
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