"He is the tallest oak in the yard and there are a lot of Democrats that want to figure out a way to chop him down," Perino told "The Story with Martha MacCallum" guest host Ed Henry Tuesday.
The first debate of the Democratic primary season will be split into two nights, June 26-27. The second night features most of the high-polling candidates on the stage, including Biden.
"The Daily Briefing with Dana Perino" host said fellow 2020 hopefuls could take the opportunity to try to paint Biden as the past and follow the path of former Presidents Bill Clinton and Barack Obama by pitching future and progress to the Democratic base.
"Next week at the debates when they start for the Democrats you will see that the shots being taken, not just at Donald Trump... They'll all do that. But there is going to be a movement for example like a Pete Buttigieg, who's trying to say that we want the party to go forward. Biden wants to take you backward," Perino said.
"And most Democrats the ones who have done very well just think in the past Bill Clinton and Barack Obama. What were their big campaign slogans -- hope and change, moving forward."
The comments came after Biden said he can win states no Democrat has won in presidential elections in decades.
"I plan on campaigning in the South. I plan on -- if I'm your nominee -- winning Georgia, North Carolina, South Carolina, believe it or not,” Biden vowed Monday, as he spoke at a gathering in the nation’s capital of the Poor People’s Campaign's Moral Action Congress.
No Democrat has carried South Carolina in a presidential election since Jimmy Carter more than four decades ago. Biden, who has developed deep ties over the years in the state where he often vacations, enjoys a large lead over his primary rivals in the state’s crucial first-in-the-South presidential primary.
But capturing the conservative state in a general election would be a high hurdle. Republicans have won the state in every presidential election dating back to 1968, except for Carter’s victory in 1976.
No Democrat has won Georgia since Bill Clinton in 1992. And other than Barack Obama’s victory in 2008, North Carolina has been solidly in the GOP column in each presidential election dating back to 1968.