This feeding trial was conducted to evaluate the effects of replacing soybean meal with brewer's dried grain levels on the growth performance, body composition, serum biochemical indices and antioxidant capacity of juvenile hybrid tilapias (s). Five hundred and forty juveniles with an initial weight of (3.00±0.08) g were randomly divided into six groups with three replicates of 30 fish. Six isonitrogenous and isoenergic experimental diets were formulated to contain different levels of brewers' dried grains to replace soybean meal at 0, 20%, 40%, 60%, 80% and 100%, respectively. The experiment was performed for 60 d in an indoor recirculating culture system. The results showed that there were no significant differences in weight gain, specific growth ratio, feed efficiency and protein efficiency ratio when the replacement level was 0-40% (>0.05). The growth performances of the fish were significantly poorer in 60%, 80% and 100% groups (<0.05). Based on weight gain and feed efficiency of broken-line analysis, the best replacement ratios of soybean meal with brewer's dried grain were 27.0% and 28.9%, respectively. The crude protein and lipid contents in the whole body and muscle decreased as the replacement level increased. When the replacement level was 100%, the crude protein and lipid contents in the whole body were significantly lower than those in the control group (<0.05). In addition, the viscerosomatic index (VSI) of the fish decreased with increasing dietary brewer's dried grain level, as did the condition factor (<0.05). The activity of alanine aminotransferase (ALT) significantly increased as the replacement level increased; when the replacement level was more than 60%, serum ALT activities were significantly higher than those in the control group (<0.05). Aspartate aminotransferase activities significantly increased as the replacement level increased (<0.05). The glucose contents were significantly reduced with increasing dietary replacement level (<0.05). The serum total antioxidant capacity (T-AOC) decreased with increasing dietary brewer's dried grain level; when the replacement level was more than 20%, the T-AOC was significantly lower than that in the control group (<0.05). Serum superoxide dismutase activities significantly decreased as the replacement level increased (<0.05). Based on the results of growth, serum biochemical indices and antioxidant capacity, the optimal replacement level was 27.0%-28.9% for juvenile hybrid tilapias.