<p>The adaptation of fish to salinity is related to a series of life activities such as fish survival, growth, and reproduction. Tilapia is considered to be an euryhaline fish. In the present study, we comparatively analyzed the salt tolerance of three tilapia species (strains) representative in Chinese aquaculture, using 60&#xa0;days’ growth experiments followed by examination of blood physiological and biochemical indicators, and expression of genes associated with salt tolerance and growth. In this study, the tilapia can grow well in saltwater with salinity up to 25‰ after specific acclimation. Among them, the weight gain rate of the genetically improved farmed tilapia (<i>Oreochromis niloticus</i>, GIFT) in the saltwater group was the highest, reaching 189.7%, which was higher than that in freshwater group, and the same was true for Blue tilapia (<i>Oreochromis aureus</i>, OA), and only the weight gain rate of the Nile tilapia Egypt strain (<i>Oreochromis niloticus</i>, ON) freshwater group is higher than that in the saltwater group. However, the survival of all three tilapia species (strains) in saltwater decreased, with the OA being the highest and the GIFT being the lowest. The results of blood biochemical analysis showed that the nutrient consumption and organ damage of the three tilapia species (strains) were different when they were subjected to long-term salinity stress. The analysis of differences in physiological and biochemical parameters (GLU, ALT, SOD, TC, GH) among three tilapia species (strains) under saltwater and freshwater conditions suggests a preliminary conclusion regarding their salt tolerance hierarchy: OA &gt; GIFT &gt; ON. The results of related gene expression supported the above conclusions. Our study provides an improved understanding of salt tolerance in tilapia and breeding of salt-tolerant tilapia species.</p>