AbstractThis 62-d research aimed to evaluate the effects of dietary lysine levels (DLL) and salinity on growth performance and nutrition metabolism of genetically improved farmed tilapia (GIFT) juveniles (Oreochromis niloticus). Six diets with lysine supplementation (1·34, 1·70, 2·03, 2·41, 2·72 and 3·04 % of DM) were formulated under different cultured salinities in a two-factorial design. The results indicated that supplemental lysine improved the specific growth rate (SGR) and weight gain (WG) and decreased the feed conversion ratio (FCR). Meanwhile, the fish had higher SGR and WG and lower FCR at 8 ‰ salinity. Except for moisture, the whole-body protein, lipid and ash content of GIFT were increased by 8 ‰ salinity, which showed that DLL (1·34 %) increased the whole-body fat content and DLL (2·41 %) increased whole-body protein content. Appropriate DLL up-regulated mRNA levels of protein metabolism-related genes such as target of rapamycin, 4EBP-1 and S6 kinase 1. However, 0 ‰ salinity reduced these protein metabolism-related genes mRNA levels, while proper DLL could improve glycolysis and gluconeogenesis mRNA levels but decrease lipogenesis-related genes mRNA levels in liver. 0 ‰ salinity improved GLUT2, glucokinase and G6 Pase mRNA levels; however, sterol regulatory element-binding protein 1 and fatty acid synthase mRNA levels were higher at 8 ‰ salinity. Moreover, 8 ‰ salinity also increased plasma total protein and cholesterol levels and decreased glucose levels. These results indicated that the recommended range of lysine requirement under different salinity was 2·03–2·20 % (0 ‰) and 2·20–2·41 % (8 ‰) and 8 ‰ salinity resulted in higher lysine requirements due to changes in the related nutrient metabolism, which might provide useful information for designing more effective feed formulations for GIFT cultured in different salinity environment.