Inroduction & Objective: Emerging contaminants of nanoparticles in aquatic ecosystems cause stress response in aquatic animals and decrease their immune function. Therefore, use of immune stimuli such as prebiotics is very necessary. The aim of this study was to investigate the effect of different levels of prebiotic Pleurotus ostreatus on hematological indices of tilapia exposed to silver nanoparticles. Materials and Methods: 120 fish were distributed for 42 days in 4 treatments (3 replicates): control (1), no prebiotic fungi, treatment (2) food containing 0. 05, treatment (3) food containing 0. 1 and treatment (4) food contained 0. 2% prebiotic. Then, 0. 5 ppm of silver nanoparticles was exposed to each group for 16 days and blood parameters were examined. Results: Prebiotic alone had no significant effect on erythrocyte count, mean cell volume (MCV), mean cell hemoglobin (MCH), mean erythrocyte hemoglobin concentration (MCHC), hematocrit, hemoglobin, white blood cell (P <0. 05) but exposure to silver nanoparticles and prebiotic in combination increased the mentioned factors compared to the control and prebiotic treatments alone. However, the levels of white blood cells and erythrocytes, hemoglobin, hematocrit, and MCH were higher than the other treatments in the combination of 0. 2 prebiotic and silver nanoparticles. Conclusion: Oral probiotics stimulate non-specific immunity in tilapia, the combined use of nano-silver and prebiotic mushrooms increase the amount of blood indices and reduce the destructive effects of nanosilver on blood indices. It is concluded that the 0. 2% prebiotic level could have the best effect on the blood indices of tilapia.