Murphy, who played Shellie in bringing the Frank Miller comic to the big screen, told Moviehole.com she's "absolutely thrilled" about reprising the role.
"It's exciting to be a part of something so big and artistically groundbreaking", Miller said. "I love the film and I'm ecstatic to be working with director Robert Rodriguez and the crew again."
Mickey Rourke has also agreed to a second go-round as villain, Marv, Moviehole said.
Murphy will be ubiquitous in the coming months with no less than five projects coming out.