McShane will play Hellboy's adoptive father, Professor Trevor Broom, reported Variety.
Harbour will star as the titular demonic hero from Mike Mignola's comic books in the new film, titled "Hellboy: Rise of the Blood Queen."
"The Descent" helmer Neil Marshall is on board to direct the project.
The new story sees Harbour's hero squaring off against a sorceress who seeks to destroy humankind.
The project is eyeing a September start and will shoot in the UK and Bulgaria.