Soybean antigen proteins (soybean glycinin and -conglycinin) are the main anti-nutritional factors in soybean meal. Recent studies showed that a high level of glycinin and -conglycinin in soybean meal can disrupt the intestinal tissue structure, resulting in digestion and absorption disorders, stunted growth, and allergic reactions with a variety of non-specific and specific immune responses in aquatic animals. In recent years, fermented soybean meal has been increasingly used in aquatic animal feed. Compared to soybean meal, anti-nutritional factors, particularly soybean antigen proteins in fermented soybean meal, are drastically reduced. This study was conducted to compare the effects of soybean meal (SBM) and fermented soybean meal (FSBM) on the growth, serum biochemical indices, gene expression, and oxidative status in and evaluate whether the effects were caused by soybean antigen protein. Practical diets (T15, TF) and purified diets (AP0, AP5) were formulated for the feeding trial. Compared to T15 (21.5% FM, 15.45% SBM, 15% FSBM), the soybean meal was completely replaced with fermented soybean meal in TF, while AP0 and AP5 were semi-purified diets containing approximately the same content of soybean antigenic protein as TF (nearly 0% soybean antigen proteins) and T15 (approximately 5% soybean antigen proteins), respectively, with soybean antigen proteins included as the sole anti-nutritional factor. Giant river prawns with an initial average body weight of (0.17±0.02) g were cultured in net cages in a fixed indoor cement tank and fed the above four diets for 64 days. The results showed that as soybean antigen proteins were reduced, trypsin activity was decreased for both series of diets. The practical diet groups showed a significantly decreased growth rate, while the purified diet groups did not, demonstrating that 5% soybean antigen protein did not affect the growth of . In contrast, a significant reduction in soybean antigen protein in the practical diet was not conducive for growth. A certain amount of soybean antigen protein increased trypsin activity to promote digestion of the feed, which in turn had a positive impact on growth. In the practical diet groups, there was no significant difference in the serum malondialdehyde content and expression of nuclear factor-κB mRNA in the gills. Superoxide dismutase activity in the serum was significantly higher in TF, while expression of the Toll-like receptor in the gills and HSP70 mRNA in the hepatopancreas was significantly decreased. In the purified diet groups, there was no significant difference in the serum superoxide dismutase activity, malondialdehyde content, and HSP70 mRNA expression in the hepatopancreas, while expression of the Toll-like receptor and nuclear factor-κB mRNA in the gills was significantly higher in the AP0 group. The results showed that fermented soybean meal scavenged free radicals by synthesizing antioxidant enzymes and reducing oxidative stress in the hepatopancreas, which may not be directly related to the reduction of soybean antigen protein content. Soybean antigen proteins and a variety of anti-nutritional factors together likely stimulate the body's immune system and promote immunity by decreasing Toll-like receptor and nuclear factor-κB mRNA expression levels. Total protein in the serum was significantly decreased in the practical diet groups, and aspartate aminotransferase activity was significantly increased. However, total protein and albumin levels were significantly decreased in the purified diet groups. The results demonstrated that this concentration of antigen proteins improved the health of the hepatopancreas and the body's amino acid and protein synthesis metabolism. In addition to a more sensitive immune response, the T15 group showed better growth performance in the practical diet groups. In conclusion, was tolerant to 5% of soybean antigen protein, which was beneficial for its growth and health. A synergistic effect between soybean antigen protein and other anti-nutritional factors likely occurred. Low levels of soybean antigen proteins in the feed led to reduced protein synthesis and metabolism in the hepatopancreas and decreased growth. These results suggest that fermented soybean meal and soybean meal can be mixed together in an appropriate proportion under normal feeding conditions.