The actress and comedienne has been hired to play a junior doctor on the Fox medical drama, according to Entertainment Weekly's Inside TV blog.
Yi's previous credits also include guest appearances in 30 Rock and Cold Case. She also appeared in the pilot of short-lived NBC series Love Bites.
Her screenwriting debut Paper Heart, in which she starred alongside Michael Cera, won a screenwriting prize at 2009's Sundance Film Festival.
Other recent cast additions include Odette Annable, who appeared in Brother & Sisters as a love interest for Justin Walker, played by her real-life husband Dave Annable.
House lead Hugh Laurie recently admitted that cast and crew are missing co-star Lisa Edelstein, who left the show in May.
House will return on October 3 at 9/8c on Fox.
Watch Charlyne Yi and Michael Cera in a scene from Paper Heart below: