mTOR signal pathway plays a vital role in the regulation of animal growth and development. In this study, growth rates of Oreochromis niloticus at different salinities were compared in a 30-day experiment; in the meantime, expression changes of downstream pathway regulation factors p70s6k and 4ebp1 were evaluated at both mRNA and protein levels. The results showed that salinity significantly inhibited the growth of Nile tilapia, the final body weight decreased with the salinity increase, and average body weight at 0, 15, 20, 25 salinity was (0.48±0.13)g/d, (0.31±0.09)g/d, (0.14±0.08)g/d, (0.09±0.03)g/d, respectively. The p70s6k mRNA expression level decreased with salinity increasing, the highest was detected at 0 salinity, while the lowest was at 25 salinity, which was significantly lower than that at 0, 15 and 20 salinities. The 4ebp1 mRNA expression at 25 salinity was significantly higher than 0, 15, 20 salinity, increasing with salinity levels. Western blot results showed the protein level of p70s6k at 0 salinity was significantly higher than that at other higher salinities, while 4ebp1 at 25 salinity was significantly higher than that at other lower salinities. Our result suggested salinity may affect growth of O. niloticus through mTOR signaling pathway.