A partial skull of a large mosasaur was discovered eroding from the upper Campanian shales of the DeGrey Formation of the Pierre Shale Group from Gregory County, South Dakota. Although the skull is not complete, sufficient characters exist to indicate that the specimen represents the first undisputed North American occurrence of the large tylosaurine mosasaur Hainosaurus, otherwise best known from the Maastrichtian of Europe. Diagnostic characters include relatively laterally compressed, symmetrical teeth with finely serrated carinae, an interlocking premaxillary-maxillary suture, a very large alar opening of the quadrate, a distinctly laterally deflected quadrate shaft, a nontriangular centrum outline of anterior caudal vertebrae, and, in particular, a pineal opening bordered by the frontal and parietal. Features of the quadrate indicate that the South Dakota specimen represents a new species of Hainosaurus, which is described herein.