We present a large, fragmentary skull and the humerus of a mosasaur (Squamata, Mosasauroidea) recovered from upper Maastrichtian beds of the López de Bertodano Formation in Marambio (=Seymour) Island, Antarctica. The material belongs to a large, adult individual with marked heterodonty as well as unusual humeral features. Different phylogenetic analyses returned the studied specimen within the Tylosaurinae, while the distinctive features of the skull and humerus allow distinguish it from the unique Antarctic known tylosaurine species, Taniwhasaurus antarcticus (Novas et al., 2002), as well as from other known Late Cretaceous mosasaurids from the Southern Hemisphere, thus, justifying the erection of a new taxon, Kaikaifilu hervei gen. et. sp. nov. The different dental types documented in the specimen studied have been previously recorded through isolated teeth from the same locality and were subsequently referred to several genera. This new find is relevant for assessing the previously known fragmentary records of Antarctic mosasaurids, suggesting that its local diversity could be more reduced than previously interpreted. The new material represents the youngest occurrence of tylosaurines in Antarctica.