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Supplementation of phosphorus nanoparticles is a promising strategy to reduce water pollution, improve phosphorus concentration in fish diet, and provide better production quality. We used 300 fingerlings of Nile tilapia that were randomly distributed into 3 groups; each one was attributed to 5 replicates of 20 fish per aquarium with initial weight (gm) (156 ± 1.25). The first diet contained traditional Di-calcium phosphate (D-group), the second supplemented with phosphorus nanoparticles in a dose equal to the previous conventional one (N-D group), and the last one included with phosphorus nanoparticles with the half dose of the conventional phosphorus group (1/2 N-D group). After 3 months of feeding, the N-D group showed the best growth performance including its feed conversion ratio (FCR), feed intake (FI), or body weight gain (BWG). Furthermore, the growth-related gene expression findings considering growth hormone receptor (GHR) and insulin-like growth factor-1 (IGF-1) were upregulated as well. Moreover, whole body chemical composition revealed higher Fe, Zn, P, and crude protein level in the N-D group than the other two groups. Lipoprotein lipase (LPL) and fatty acid synthetase (FAS) mRNA expression showed a significant increase in 1/2 N-D and N-D groups compared with the control group. To sum up, using of nano-phosphorus particles improved the growth rate and immunity response of Nile tilapia, besides decreasing water pollution.