Fish meal (FM) is a significant source of protein, but the high cost has limited its use in feeds. Hence, alternative, economic and available FM substitutes should be found. In this study, the consequences of replacing FM with rice protein concentrate (RPC) on the growth parameters, proximate body composition, digestive and absorptive capabilities, biochemical parameters and the expression of appetite-related gene (ghrelin) in Nile tilapia, Oreochromis niloticus, were investigated. Fish (27.8 ± 0.1 g) were randomly organized into four groups and fed on experimental diets having four replacement percentages of FM with RPC: 0%, 25%, 50% and 75% (RPC0, RPC25, RPC50 and RPC75) for 5 months. The results cleared that RPC25 group exhibited linearly and quadratically the highest values for growth parameters, growth hormone level, and activities of protease, amylase as well as proximal intestinal villus length, width, the goblet cells count and ghrelin gene expression among all groups. From overall results, RPC could be used as an economically and beneficial ingredient to replace up to 25% of dietary FM in Nile tilapia diet with enhancing the growth performance, digestive and absorptive capability, and health status, but with the supplementation of synthetic amino acids.