"I was already imprisoned as innocent person in Italy, and I can't reconcile the choice to go back with that experience," Knox said in an interview with Matt Lauer on NBC's "Today" show. "I just can't relive that."
Lauer asked Knox if she worried that she was handing prosecutors an admission of guilt by not attending the trial.
The Seattle native replied, "I look at it of an admission of innocence, to be quite honest."
Knox said there was no trace of her in the room where her roommate, Meredith Kercher, was found killed when both were exchange students studying in Perugia, Italy. Kercher's throat had been slashed. "It's impossible for me to have participated in this crime if there's no trace of me," Knox said.
She said school and finances also were keeping her from attending the trial, which is scheduled to begin in Florence on Sept. 30.
In March, Italy's supreme court ordered a new trial for Knox and her former Italian boyfriend. An appeals court in 2011 had acquitted both, overturning convictions by a lower court. Italian law cannot compel Knox to return for the new legal proceeding.
Knox said Friday that she still had faith in the Italian legal system.
"I believe that people who really care about justice and look at this without prejudice will come to same conclusion," she said.
Still, she acknowledged that the prospect of returning to prison haunted her.
"I thought about what it would be like to live my entire life in prison and to lose everything, to lose what I've been able to come back to and rebuild," she said. "I think about it all the time. It's so scary. Everything is at stake."