Biofloc technology (BFT) is a zero-water exchange, environmentally friendly aquaculture system that is now widely used since it is proven to enhance the growth and immunity of farmed fish. Gibel carp (also known as Prussian carp) is a major aquaculture species in China, especially around Yancheng in Jiangsu Province, and it is also grown in mudflats. Developing an effective aquaculture system for gibel carp is also helpful for exploring mudflats usage in fish aquaculture. However, sudden outbreaks of disease have become a great and common threat to carp-farming operations, as this causes huge economic losses. Since 2009, an epizootic with severe mortality rates caused by cyprinid herpes virus 2 (CyHV-2) has emerged among cultured gibel carp in China, especially in the northern part of Jiangsu Province. The disease develops fast, spreads widely to almost all main areas of gibel carp, and mortalities may reach 90%-100%. Thus, disease becomes a limiting factor for aquaculture, yet effective methods to prevent or control CyHV-2 are lacking. In order to discuss the practical usage of BFT in mudflat fish culture in terms of disease prevention, this study subjected the representative species (gibel carp) to the disease, using fish cultured in two different systems: in a BFT system without any water exchange, and in a common recirculating system with 1/4-1/3 water exchange daily (as control), to analyze the effect of BFT on growth performance and disease resistance in this carp. Growth factors, digestive enzymes, and immune-related enzyme activities were detected by common methods using commercial kits; heat-shock protein 70 (HSP70) mRNA relative expression was analyzed with qRT-PCR; and disease resistance against bacterial infection was evaluated by challenge tests. The results demonstrated the following: (1)The rates of weight gain, specific growth, and survival of the gibel carp in the BFT group were significantly higher than occurred for fish in the control group (<0.01); however, the condition factor and viserosomatic ration did not significantly differ between the two groups (>0.05). (2)The activity of digestive enzymes (i.e., amylase, lipase and protease) in the BFT group was significantly enhanced (by 53.10%, 28.10% and 17.99%, respectively) in comparison with the control group (<0.05). (3)The super oxide dismutase activity in skin mucus, total antioxidant capacity in liver, and lysozyme in serum were significantly induced in the BFT group (<0.01). (4)HSP70 mRNA relative expression in the BFT group was up-regulated 1.29-, 1.34-, 1.87-and 1.68-fold in the spleen, kidney, liver and gill, respectively. (5)Disease resistance against bacterial infection was improved in the gibel carp eventually challenged by . The cumulative mortalities of gibel carp cultured in the BFT system after experimental injection with bacterial concentrations of 4.2×10⁷ CFU/mL, 4.2×10⁶ CFU/mL and 4.2×10⁵ CFU/mL, were 62.5%, 25%, and 0 within 7 days, respectively. These values were much higher than those detected among fish in the control system (i.e., 75%, 37.5% and 12.5%). This study demonstrated that BFT can improve growth performance, digestive enzyme activity, and disease resistance of gibel carp, and that BFT could be successfully more often used in mudflat fish aquaculture. We suggest that future studies with gibel carp cultured in BFT systems should investigate the optimum concentrations of total suspended solids, prebiotics specialized for mudflat fishes, and relevant molecular immune mechanisms.