This study was planned to investigate the effect of commercial nisin on the quality and safety indices of the frozen cultured Nile tilapia fillets. Fresh tilapia fillets were treated with different concentrations of nisin (0.1, 0.15, and 0.20%) for 30min, compared to the control (untreated), packed and stored at -18°C for three months. Results showed that the highest inhibition zone of nisin was found in the case of Bacillus cereus compared to other Gram-positive bacteria and Escherichia coli compared to other Gram-negative bacterial strains. In addition, investigated safety and quality indices showed that farmed raw tilapia fillets were lower than the permissible limits (MPLs). During frozen storage periods, fish fillets treated with nisin especially 0.2% could be controlled with respect to protein and fat decomposition since the values of pH, TVB-N, TMA, and TBA were more acceptable than those of the control sample. In addition, the nisin level could reduce the microbiological aspects (total viable count, psychrophilic, coliform group, yeasts, and molds) compared to the control. In conclusion, commercial nisin, especially at 0.20% could control the change rate of hygienic quality indices of farmed tilapia fillets throughout frozen storage periods. Thus, commercial nisin as a bio-preservative is recommended to improve the safety and quality of fish products.