Anderson will team up with Australian director Benedict Andrews to work on the play, which will hit the stage at London's Young Vic theatre next summer (14).
The Young Vic's artistic director David Lan tells British newspaper the Daily Mail, "This was Gillian and Benedict working together. They sought each other out, and went through what they'd like to do, and came up with Blanche. With these two people involved there are going to be fireworks on the stage."
The X-Files star began her career in theatre before finding fame on the small screen, but has not taken on a high-profile role in several years.
Blanche DuBois was famously portrayed by Gone With The Wind star Vivien Leigh, who played the role both on the London stage and in the 1951 film adaptation, while other stars to have tackled the southern belle include Cate Blanchett, Faye Dunaway and Rachel Weisz.