In conclusion, in C. japonica the up-regulation of immune related genes-FGA, AHSG, MPP1, KNG, A2M, FGB and FGG-was simultaneously stimulated by berberine hydrochloride. Bioinformatics analysis showed that these genes may activate the immune complement system in the hemolymph. This is the first report of transcriptome analysis of related immune gene responses under the action of berberine hydrochloride in crustaceans. In particular, LZM, ACP, and AKP were revealed as key enzymes playing a positive role in the immune response caused by berberine hydrochloride. These findings will contribute to improving the understanding of the molecular mechanisms related to berberine hydrochloride in crustaceans, and to the development and application of treatments using this bioactive compound in aquaculture.