In connection with the global demand for safe human food and the production of environmentally friendly aquaculture products, acidifiers are natural organic acids and salts that have received considerable attention as animal-feed additives. The current study was designed to evaluate the effects of potassium diformate, KDF, on the growth performance and immunity of cultured Oreochromis niloticus, O. niloticus. Four iso-nitrogenous and iso-caloric rations containing graded levels of KDF, including 0% (control basal diet), 0.1%, 0.2% and 0.3%, were fed separately to four equal fish groups (30 fish/group with an initial body weight of 53.49±6.15 g) for sixty days. At the end of the experimental period, the fish groups fed on 0.2% and 0.3% KDF exhibited significant improvements in their feed intake, live weight gain, specific growth rate, feed conversion ratio and protein efficiency ratio, with concomitant improvement of their apparent protein digestibility (p<0.05). Dietary supplementation of 0.3% KDF appeared to stimulate the beneficial intestinal flora; a proliferation was observed of indigenous probionts (Eubiosis) associated with the relative activation of cellular and humeral innate immunity (phagocytic activity/index, nitroblue tetrazolium reduction test and serum/gut mucous lysozyme activity). The cumulative mortality of the fish groups fed on KDF and challenged orally with Aeromonas hydrophila was lower than that of the control group. The resistance against diseases increased with dietary KDF in a dose-dependent manner. Thus, we conclude that the use of acidifiers can be an efficient tool to achieve sustainable, economical and safe fish production.