The greater amberjack (Seriola dumerili) is a kind of widely distributed and economically important saltwater fish. However, its growth and development are sensitive to alterations of marine environment, for example, seawater salinity. Previous studies have unraveled the contributions of transcriptional regulations in modulating the resistance to seawater salinity fluctuations in the greater amberjack, but no attentions have been ever paid to post-transcriptional mechanisms, which also play an important role in fish growth, development and adaptation to environmental stress. In this study, we performed a comparative transcriptomic analysis to investigate the genome-wide alternative splicing (AS) dynamics in the greater amberjack under both hypo- (10 ppt) and hyper-salinity stresses. In the gills, 461 and 426 differential spliced genes (DSGs) were identified in response to 10 ppt and 40 ppt salinity, respectively. For both stress scenarios, the genes related to sodium ion transport were prone to produce a higher proportion of isoforms including more exons, suggesting an enhancement of mainly involved in. GO enrichment results showed that these genes were mainly involved in sodium ion adjustment in response to the deviation of optimal water salinity. Comparatively, pH regulation, developmental process, and positive regulation of Wnt signaling pathway were exclusively activated under 10 ppt salinity, while lipid transport and regulation of cell division were enhanced when exposed to 40 ppt saline. In the kidneys, 468 more-exon inclusive DSGs were found in response to both hypo- and hyper-salinity stress, which mainly associated with antioxidant processes, such as sulfur compound biosynthetic process and peroxisome organization. Furthermore, AS events were found to modulate different physiological processes from gene expression, suggesting AS played relatively independent role in salinity stress response in the greater amberjack. These novel findings provide us a better understanding of the post-transcriptional mechanisms underlying the resistance of the greater amberjack to ambient salinity oscillation and also provide a genetic basis for the conservation of marine organisms and biodiversity.