The different mechanisms adopted among various aquatic animals in countering salinity stresses are fundamental in determining their niche and distribution. To date, most of our knowledge on these differences, especially in terms of genetic regulation, is mainly derived from the osmoregulatory studies in fishes. Here, four chordates (amphioxus, goldfish, lamprey, sea bream) which have striking differences in their halotolerance levels, were compared for their transcriptomic responses after treatments at different salinities. Contrary to common expectation, instead of identifying a core set of differentially expressed genes shared commonly among these investigated chordates, only three gene families (serine/threonine protein kinase, protein-tyrosine kinase, and phospholipid-translocating ATPase) were found to be regulated in the same manner in lamprey, goldfish, and sea bream. The results suggest that the osmoregulatory systems and abilities are under high selection pressure, which results in fast and independent evolution in deuterostome lineages, and contributes to their diversified adaptations in different environments.