But the American also said that everything was at stake and that she does think about what would happen if she were found guilty.
Knox served four years of a 26-year sentence in an Italian prison for the 2007 murder of her British roommate Meredith Kercher, whose half-naked body was found in a pool of blood in the house the two shared as students in the town of Perugia.
After an appeal, Knox and her Italian ex-boyfriend Raffaele Sollecito were acquitted in 2011 of the crime prosecutors attributed to a sex game gone wrong.
"I was already imprisoned as an innocent person in Italy and I can't reconcile the choice to go back with that experience," Knox said in an interview with NBC's Today show.
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"I look at it as an admission of innocence to be honest ... It's common sense not to go back."
Knox's lawyer David Marriott told AFP last month that she would not make the trip to Italy, saying she was not required to be there.
The only person behind bars for the murder is Rudy Guede, a local drifter born in Ivory Coast who is serving a 16-year prison sentence after being tried separately and convicted of murder and sexual assault.
Knox, who returned to her home near Seattle after her acquittal, appeared confident the proceedings would end in her favor.
"I don't think I'm going to be put back in prison. I think we're going to win. That's why I'm fighting this fight," she said.
Still, Knox admitted she did think about the "worst case scenario" and what it would be like to "lose everything."
"I think about it all the time and it's so scary," she said. "Everything is at stake.