Gymnocypris przewalskii przewalskii is distributed in Qinghai Lake, the largest inland saltwater lake in China. It is the only Cyprinidae fish in the Qinghai Lake water system and has extremely strong adaptability to the ecological environment with high salinity. G. p. przewalskii originates from the freshwater species Gymnocypris eckloni eckloni in the Yellow River and has a freshwater subspecies, Gymnocypris przewalskii ganzihonensis, distributed in the Ganzi River. Therefore, G. p. przewalskii is considered an ideal material for studying the high salt adaptation of plateau fish. Previous studies have characterized the evolutionary basis of highland adaptation in G. p. przewalskii; however, its adaptability to highly saline aquatic environments remains elusive. In the current study, we performed physiological, histological, genomic and transcriptomic analyses to investigate the phenotypical adaptation of G. p. przewalskii to a high saline environment and the underlying genomic and regulatory bases.