An 8-week feeding trial was implemented to evaluate the effects of replacing fish meal (FM) with mussel (Cristaria plicata) meat (MM) on growth, digestive ability, antioxidant capacity and hepatic insulin-like growth factor I (IGF-I) gene expression of juvenile Ussuri catfish (Pseudobagrus ussuriensis). Three isonitrogenous and isolipidic diets were formulated to include 0, 177.5 and 355.1 g/kg of MM, accordingly, replacing 0% (M0, control), 50% (M1) and 100% (M2) of FM protein, respectively. The results showed that the final body weight, weight gain, specific growth rate and feed intake were gradually decreased with dietary MM protein levels increased, but there were no significant difference between M0 and M1 groups (p > 0.05). The protein efficiency ratio was increased significantly with dietary MM inclusion (p < 0.05). The apparent digestibility coefficient of dry matter, crude lipid and gross energy gradually increased with increasing dietary MM protein levels, but the apparent digestibility coefficient of crude protein was not significantly affected by MM protein supplementation (p > 0.05). Fish fed diet, M0 and M1 remained unaffected significantly on activities of alpha-amylase and pepsin (p > 0.05), but fish fed diet M2 had the highest activities of alpha-amylase and pepsin. Fish fed diet M1 or M2 had significantly lower hepatic total antioxidant capacity, superoxide dismutase and the higher malondialdehyde level compared to fish fed diet M0. In addition, no significant difference was observed in hepatic IGF-I gene expression level for fish fed diet M0 and diet M1, and fish fed diet M2 showed significantly lower hepatic IGF-I gene expression level. Therefore, we can conclude that MM protein can successfully substitute 50% of FM protein without significantly negative effect on growth, nutrient utilization, and hepatic IGF-I gene expression for juvenile Ussuri catfish, but the antioxidant capacity was negatively affected in the present study, what is more, the total replacement of FM by MM in diet may result in the inhibition of the growth and antioxidant capacity of fish.