Cheryl will begin her run in the role from 21 January and will be on stage for a 14-week run at London's Lyric Theatre.
Also joining her in the production is Hugo Chegwin from People Just Do Nothing, Louise Ford and Scott Karim.
The singer has previously acted before, first in the 2007 remake of St Trinian's and most recently in an adaptation of Four Kids and It alongside Michael Caine.
In a statement, Cheryl said of joining the play: "I am really excited to be taking part in what is such a new challenge for me. I have always loved and been a big fan of theatre so I’m especially excited to be playing the role of Jenny in this production of 2:22."
She continued: "It is a brilliant role and subject matter with a very interesting plot! Danny Robins is such an intriguing character which is evident throughout this play and his style of writing has an odd sense of familiarity to me, being a fellow Geordie! I look forward to working with Matthew and the other cast members and can’t wait to get going."
She also said on Instagram: “I went to see the show with a previous cast and LOVED IT! It is a totally new and exciting experience for me so if you’re looking for a fun night out & some entertainment in your new year tickets are available now.”
2:22 A Ghost Story is about a woman who believes her new home is haunted but her husband does not believe her leaving to a clash of views during a dinner party between sceptics and believers.
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