The actress played the role of Sarah Platt on the Weatherfield drama for eight years until 2007, when she bowed out of the show to pursue new projects.
Asked by We Love Telly whether she would ever make a Corrie comeback, O'Brien replied: "Yes, maybe one day if they had a space for me. Sarah's such a big part of the Platt family - it would be nice to clear up some unfinished business. Who knows?"
The 27-year-old admitted that she became particularly keen for a return when watching the soap's 50th anniversary celebrations last month.
She said: "It's the first time that I thought - 'Oh, I wish I was there'. I really got a pang for it. I was imagining how they all must be feeling - the adrenaline and going out afterwards."
O'Brien is currently playing the role of Bex Fisher on BBC One's Waterloo Road.