While some studies have investigated the effects of dietary protein on the activities of protease in Nile tilapia, little information exists about these enzymes and hormones regulating appetite at the molecular level. Therefore, we investigated the performance, protease activities and expression of genes related to protein intake and digestion in juvenile tilapia fed with diets containing different levels of crude protein (CP): 25.14, 31.12, 36.60 and 42.05%. The fish were fed to apparent satiation three times a day for 65 days. The animal performance and the retention rates of protein and energy linearly decreased with an increase in dietary CP content. A positive quadratic effect of CP on pepsinogen was observed, although the acid protease activity was not affected. Trypsinogen and trypsin activity in the intestine presented similar patterns, showing a positive quadratic response to dietary protein levels. A linear increase in intestinal chymotrypsinogen expression was observed, but the activity of chymotrypsin showed a positive quadratic response. In addition, the expression of cholecystokinin (cck) and peptide yy (pyy) increased linearly with increasing CP. Dietary protein modulates the activity of alkaline proteases as well as the expression of these protease genes and hormones involved in appetite regulation. These changes can help expand our understanding of feed intake and digestion control, thereby improving feed formulations for this species.