The wide use of nano-sized metallic materials could result in the release of these particles into the environment. In addition, due to the dissolution of these nano-materials, some of the adverse effects could result from the dissolved metals. On the other hand, dietary supplements play a key role in improving the immunity of consumers; hence, the use of immune stimulants such as mushroom seems to be very necessary. In this study, the dietary effect of Pleurotus ostreatusmushroom was investigated on serum immunity and liver histopathological indices of Oreochromis niloticus exposed to silver nanoparticles (AgNPs). Serum total protein level enhanced with increasing prebiotic concentration. Serum immunoglobulin and albumin levels increased in the group treated with Pleurotus ostreatus. The amount of these indices significantly increased at the concentration of 0. 2 mg/kg; however, glucose value decreased in both of the experimental groups. Serum ALT and ALP levels significantly reduced in the combined treatment group (AgNPs and mushroom) at the concentration of 0. 2 mg/kg, in contrast with the control group. In the combination treatment group (AgNPs and mushroom), the serum AST level significantly reduced at concentrations of 0. 1 mg/kg and 0. 2 mg/kg; however, it increased at the concentration of 0. 05 mg/kg compared with the control group, indicating that immunological indices could improve due to the combined use of AgNPs and mushroom. The overall conclusion of this study shows that the use of mushroom at 0. 2 mg/kg in combination with AgNPs could partially improve the effect of AgNPs on tilapia.