The liver transcriptome was analyzed after 22 d culture with different salinity water using RNA sequencing (RNA-seq) in spotted scat (Scatophagus argus). The relationship between different salinity stress and lipid metabolism in livers was investigated. The difference in liver lipid metabolism is important to adapt low- and high-salinity stress in spotted scat, which has an important value for understanding the molecular basis of salinity adaptation in euryhaline fish.