The actor has landed a role as a special guest star in every episode of the show's upcoming fourth season, Showtime has announced.
Cannavale will play a hospital administrator who is described as "formidable".
His character is sent to All Saint's Hospital to improve its efficiency and financial status, but Showtime claimed that "his arrival is sure to shake things up".
Cannavale recently appeared in Blue Bloods.
He won an Emmy for his role in Will & Grace and has also worked on shows including Cold Case, Cupid and Ally McBeal.
Production on the fourth season of Nurse Jackie, which was announced in May, will begin in September. The show is due to return next year.