Abstract: An experiment was conducted to investigate the effects of replacing fish meal (FM) and soybean meal (SBM) by fermented soybean meal (FSBM) on growth performance, serum biochemical indices, and immune genes in giant river prawn, Macrobrachium rosenbergii, and to find a suitable proportion of FSBM to replace FM in diets. Five isonitrogenous and isoenergetic diets were formulated for giant river prawn, among which a basal diet (T0) containing 30% FM and 18% SBM was treated as the control group, and the FM and SBM (2﹕1) in the basal diets replaced by 2% (T2), 5% (T5), 8% (T8) and 15% (T15) of FSBM respectively were treated as experimental diets. Giant river prawns with initial average body weight of (0.17±0.02) g were cultured for 64 days in indoor net cages at a cement tank. Results showed that with increasing FSBM supplemental level, the growth rate and specific growth rate increased firstly and then decreased, and the highest value was found in group T8. Serum superoxide dismutase activity and malondialdehyde content firstly increased and then decreased. MDA of all experimental groups was higher than that of the control group. Serum aspartate transaminase, alanine aminotransferase activity and total protein content had decreasing trend followed by an increasing trend, and the values in all experimental groups were lower than the control group. Gills Toll receptor mRNA and NF-κB mRNA expression levels and hepatopancreas heat shock protein mRNA relative expression levels in group T15 were the highest among all groups. All these results indicated that the replacement of FM and SBM with FSBM would affect growth, antioxidant ability and immunity, and the optimum amount of FSBM was 8% in the diets in this experiment.