The Sisters Brothers are portrayed by Joaquin Phoenix and John C. Reilly which basically seems to be a sort of humorous combination but I don't think this is strictly a comedy. They are paid killers and they are sent to murder a gold prospector named Herman Warm but Reilly's character is having a bit of a change of heart about what he and his brother do for a living. It sounds like material that would have been great for the Coen Brothers but the film is directed by Jacques Audiard the writer and director that brought us A Prophet and Dheepan. It's apparently been a bit of a dream project for Reilly who bought the film rights for the novel back in 2011.
The book is laugh-out-loud funny, owing to the contrast between its arch, period-appropriate prose, and the dark, criminally stupid behavior of its protagonists. I hope I’m wrong, but I don’t see a way to capture that contrast in a movie. And the trailer isn’t encouraging.