Amanda Knox accused the media of creating a false narrative around her over the 2007 killing of Meredith Kercher.
Knox was making her first visit to Italy since being imprisoned and later acquitted for the murder of her British roommate.
She fought back tears while speaking at a conference event entitled "Trial by Media" in Modena on Saturday.
Knox, 31, claimed she was depicted on the global scene as "a cunning, psychopathic, dirty and drugged whore. Guilty until proven otherwise".
She added the media invented a "false and baseless story... (which) spoke to fears and to people's fantasies."
Knox and her then-boyfriend, Raffaele Sollecito, were convicted for the slaying of British student Kercher, with whom Knox lived in Perugia, in central Italy.
Both spent four years in an Italian prison before being acquitted although the legal battle, which grabbed headlines around the world, continued for a few years The Italian Supreme Court annulled their conviction for murder in 2014 but Knox had to pay damages for libel to a man she had falsely accused.
"While on trial for a murder I didn’t commit, my prosecutor painted me as a sex-crazed femme fatale, and the media profited for years by sensationalising an already sensational and utterly unjustified story," Knox wrote in a Medium article ahead of her return to Italy.
"It’s on us to stop making and stop consuming such irresponsible media," she added.