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Mushrooms have a large amount of biologically active compounds such as prebiotics. In the present study, we tested the effect of supplementing oyster mushroom powder in the diet on growth performance, survival, serum and mucus immune parameters and mucus protein pattern of Nile tilapia fingerlings. Therefore, 200 pieces of Nile tilapia fingerlings with an average weight of 9.15 ± 0.09 g were prepare and then, they were fed with oyster mushroom powder at four levels including 0, 0.5, 1 and 2 g kg-1 diet by 3% of their body weight per day (three replications). At the end of the experiment, biometry was performed to measure the growth performance. Also, some serum and mucus immune parameters such as total immunoglobulin and lysozyme were investigated. The protein pattern of skin mucus was evaluated by sodium dodecyl-sulfate polyacrylamide gel electrophoresis method. The results showed that the best growth performance and the highest levels of lysozyme and mucus immunoglobulin were significantly in the group fed with a diet containing 2 g oyster mushroom powder compared to the control group (P<0.05). The amount of lysozyme and total serum immunoglobulin was significantly higher in the treatments fed with 0.5 and 1 g of oyster mushroom powder, respectively, compared to the control group (P<0.05). The protein bands ranged from 11 to 100 kilo Daltons. The density of bands in the treatment of oyster mushroom powder was higher compared to the control group. In general, the results showed that the diet containing 2 g of oyster mushroom powder had more positive effects on growth performance, protein pattern and some immune parameters of mucus and serum of Nile tilapia fingerlings. [ABSTRACT FROM AUTHOR]