Sean Connery's career was at such a low point when he read for the role that Columbia Pictures refused to finance the movie when Jean-Jacques Annaud cast him as William von Baskerville.

According to Ron Perlman, director Jean-Jacques Annaud had purposely not written a lot of the movie's dialogue, in order to more easily secure funding. When they started filming however, he wanted Perlman to talk in all his scenes. Since Salvatore was described as a character who speaks "six languages at once" (among them Latin, Italian, German, English, and French), Perlman got copies of the book in all of those languages. He then composed mixed-language sentences by combining words from Salvatore's sentences from each book.

Christian Slater had nothing but praise for his co-star Sean Connery. He described working with Connery "like having a master class in acting, life, all sorts of things. He's an incredible professional, a real gentleman, a man's man." He also said that Connery was extremely involved in every detail of filming, and at one point scolded the on-set horse wrangler for mistreating the animals. Ron Perlman had similarly fond memories of Connery's mentoring skills and meticulous preparation, and added that Connery would "basically sit there for eight hours between shots and download [stories about Hitchcock and John Huston and all the people he'd worked with] onto me, and see the delight coming out of me." Perlman even came to the set on his days off, just to see Connery work.

William von Baskerville is amazed when he discovers a book by "Umberto of Bologna", a reference to Umberto Eco, who teaches at the University of Bologna, and is the author of the book on which this movie was based.

Sir Sean Connery lobbied heavily for the part of William of Baskerville, having his agent contact director Jean-Jacques Annaud every two months. However, Annaud was initially not keen on casting Connory, because he associated him too much with his James Bond character. Numerous other actors were considered, including: Sir Michael Caine, Albert Finney, Richard Harris, Sir Ian McKellen, Roy Scheider, Jack Nicholson, Paul Newman, Marlon Brando, Robert De Niro, Donald Sutherland, Max von Sydow, Yves Montand, Vittorio Gassman, and Frederic Forrest. Annaud couldn't find the actor he wanted among them, but he was quickly won over when Connery read for the part: "What I was hearing was what I had heard inside me for almost two years. I stopped him on page 3".