Sienna was picked out of a shortlist of six or seven actresses in Toronto. The character was somewhat controversial during pre-production, as Shinji Mikami was against the appearance of major game characters appearing in the film series, fearing their portrayal could alienate fans. This opposition died down and the Jill character was allowed in the film.
Sienna herself was not familiar with the games, and reportedly studied the character by watching playthroughs of Resident Evil 3: Nemesis. Actress Milla Jovovich suggested adding in a line to the script explaining that Raccoon City is going through an unexpected heatwave as an excuse for the cast to wear less constrictive or more revealing clothing. This was supported by the production team, as it gave a reason to have Sienna wear a tube top and miniskirt to reference Nemesis. They had earlier considered such clothing, but given up due to not finding any explanation for it. Sienna's clothing limited her movement in martial arts sequences, leading to the fight choreographers giving her more punching and gun play.
After the film's release, Sienna was asked to reprise her role for Resident Evil: Extinction. She turned it down due to scheduling conflicts with the 2006 fantasy film Eragon, where she appeared alongside Extinction actor Chris Egan. Sienna also briefly reprised her role as Jill in a post-credits scene for the 2010 film Resident Evil: Afterlife. Her final appearance in the franchise was in the 2012 film Resident Evil: Retribution, where she played one of the antagonists as a Jill under mind control similar to Resident Evil 5.