Traditionally, fish oil is the main lipid source in the feed for most species in aquaculture owing to its effective supply of energy and high content of essential fatty acid. The fatty acid especially n-3 HUFA from the fish oil had also been proved to have positive effect on maintaining the immune system. However, the decline of fish oil production from wild fisheries has resulted in a supply shortage and price escalation of fish oil. Therefore, it has been a major challenge to find viable sources of oil to substitute fish oil. Among available vegetable oils, soybean oil has been widely chosen due to its availability, price and abundant content of fatty acid. In this study, we evaluated the effects of diets with different fish oil and soybean oil ratios on grouth, non-specific immune response and disease resistance in Chinese mitten crab (). Five isonitrogenous and isoenergetic diets were formulated in which 0% (control: F1), 25%, 50%, 75%, or 100% (F2−F5) of the fish oil was replaced with soybean oil. Juvenile crabs (mean weight 0.27±0.03 g) were assigned to one of five treatment groups (four replicates per group) and fed one of the diets for 42 d. There was no significant difference in the survival rate among the treatments (0.05). The weight gain was significantly higher in the F4 group than in the F1 group (0.05). Similarly, the crabs in the F4 group had significantly higher serum ACP (acid phosphatase), AKP (alkaline phosphatase), and serum SOD (superoxide dismutase) activities than the other treatment groups (0.05). F4 and F3 group were significantly higher than the other groups (0.05). Serum MDA (malondialdehyde) content was significantly higher in the F1 group than in the other groups, but there was no difference between the other groups (0.05). Serum PO (phenoloxidase) activity was higher in F4 and lower in F5 than the other groups (0.05). There was no difference in serum lysozyme activity among the groups (d. The first death was recorded in F5, and the crabs in F5 had significantly higher cumulative mortality than those in F1 and F4 (0.05), but there was no significant difference among the other groups (0.05). In conclusion, complete substitution of fish oil with soybean oil did not affect growth performance, but did reduce the ability to resist disease. Our results suggest that replacement of 75% fish oil with soybean oil in the diet of Chinese mitten crab can improve growth with little effect on disease resistance.