The annual San Diego convention kicks off on Wednesday night (July 11), but fans of the series are already in town for the final film's last panel on Thursday (July 12).
A report first emerged on Twitter stating that the fan, known as G, was struck by a car while crossing the street outside the convention centre, according to Examiner.
"If you pray pls do so now for Twi fan G! She was just hit by a car in front of the convention centre! She was unconscious when taken hosp," wrote one attendee.
Another added: "From the moment she was hit to when the ambulance arrived and took her, she was completely unconscious.
"I don't know if it's super serious but it might be if she was knocked off her feet and left unconscious. Everybody is pretty shaken up about it."
The first attendee later wrote that G had died from the injury: "Im sorry to tell everyone G passed away."
Police confirmed that there was an incident on Harbor Drive at 9.20am on Tuesday (July 10). Officials stated that a 53-year-old woman in town for the convention tried to run across the street, but tripped into an oncoming Subaru.
A statement from Summit Entertainment and Lionsgate read: "Lionsgate, Summit and the entire Twilight community are saddened by the death of a Comic-Con fan today due to a traffic accident during the hours leading up to this year's convention in San Diego.
"Our thoughts and condolences go out to the victim's family and friends. She will be respectfully remembered this Thursday (July 12) in Hall H."
Comic-Con runs from July 11 to July 15.