"If he continues to predicate the actions that we take on a false premise, then we're in further danger," Pelosi said during a wide-ranging interview on "This Week" with ABC News' Chief Anchor George Stephanopoulos.
Pelosi also referred to Trump's comments at the onset of the crisis, in February, when he told reporters that the novel coronavirus would "disappear" like a "miracle," and that it "will go away."
"His earlier delay and denial caused deaths," Pelosi said. "So it's very important that we walk the line that is close to evidence, data, science as we go forward, and not a whimsy, magic, hoax of allegations and placing blame instead of taking responsibility."
"We cannot fight a pandemic, we cannot open up our economy based on falsehoods," Pelosi added.
Pelosi's comments come amid an ongoing war-of-words with Trump, who took to Twitter to blast the speaker, calling her an "incompetent, third-rate politician" who is "responsible for many deaths."
"Frankly, I don't pay that much attention to the president's tweets against me," Pelosi told Stephanopoulos. "As I've said, he's a poor leader, he's always trying to avoid responsibility and assign blame."
Pelosi was also critical of Trump's handling of protests that have broken out in a handful of states over shelter-in-place orders that have kept workers from their jobs.
Trump posted a series of incendiary tweets last week apparently encouraging the protesters to violate orders to stay at home.
"I think of it largely as a distraction and the president's embrace of it as a distraction from the fact that he has not appropriately done testing, treatment, contact tracing and quarantine," Pelosi said.
The roughly $350 billion small business loan program established under the $2 trillion coronavirus emergency relief package that Congress passed last month ran out of funds late last week, leaving thousands of small business owners in limbo.
Pelosi signaled that Congress is "very close" to striking a bipartisan deal on an interim emergency relief package to replenish the depleting funds in the Paycheck Protection Program.
"I think we're very close to agreement," Pelosi said, adding Democrats have an "urgency to do something for our hospitals, our teachers and firefighters."
"Everything we've done -- three bills in March -- were all bipartisan. This interim package will be too, and the businesses will have the money in a timely fashion," Pelosi said.
Congressional leaders are currently negotiating with Treasury Secretary Steven Mnuchin to get past a standoff on funding for the small business loan program. A vote in the Senate failed earlier this month over a dispute on the size and scope of the legislation.
Republicans want to boost the small business loan program with an additional $251 billion. Democrats are pushing for nearly half a trillion dollars for the emergency relief package, with funds going toward the small business loan program, local and state governments, hospitals and an increase in food benefits.
During a White House briefing on Saturday, Trump called on lawmakers to replenish the small business relief fund saying that "funding is now fully drained. It's out. It's gone."
"Lawmakers must stop blocking these funds and replenish the program without delay," Trump said. "The Democrats have to come on board. I used to read that these were Democrat programs, not Republican. Seems to have switched around a lot, hasn't it, huh? Switched around a lot. The Republicans want it. I think the Democrats probably do too, but they also want other things that are unacceptable."
While a deal may be close, voting on it is another issue. Pelosi acknowledged that remote voting by proxy, which would allow lawmakers who are unable to travel to Washington to give their proxy to a lawmaker who is in the chamber, is a possibility.
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To allow for a proxy vote would mean a temporary rules change on the House floor that lawmakers would have to vote on. If they attempt to pass a rule change under unanimous consent -- which wouldn't require every lawmaker to return to the nation's capital -- any one member of the House could potentially object and further delay passage.
"We want to make sure though that we can do it in a bipartisan way," Pelosi said.
As for reopening the nation, Pelosi wouldn't give an estimate on when she thinks Americans can return to normalcy. Los Angeles Mayor Eric Garcetti said last week that large gatherings like sporting events and concerts are unlikely to occur until 2021
"I don't know that anybody can give you a timeline," Pelosi said. "We're prayerful that there will be a cure soon, that there'll be a vaccine -- that will take longer. That's really the answer."
"And how wonderful the American people are they understand that we have to have a scientific evidence-based approach to how we go forward," Pelosi said. "Because we can't just go out there and then find out that we went out too soon."