To date, microbial endocrinology has revealed that many microorganisms have evolved specific mechanisms to sense and respond to stress hormones. Catecholamine stress hormones have been demonstrated to stimulate bacterial growth and virulence-related gene expression. In bacteria, the QseBC two-component system is widely used in signal transduction mechanisms, which have an important impact on bacterial virulence. In this signaling system, the sensor histidine kinase QseC is a bacterial receptor for the host epinephrine (Epi)/norepinephrine (NE), which activates virulence genes in response to interkingdom cross-signaling. In NJ-35, NE exhibited the strongest growth stimulation and enhanced virulence. However, it remains poorly understood whether the QseBC two-component system is involved in the recognition and response process of NJ-35 to NE. To determine whether QseC recognizes NE and regulates bacterial virulence, in this study, we constructed a ) and a complement strain ( toxicity under NE induction. Our data provide evidence that the growth-promoting effect of NE on Δ was significantly higher than that of the wild-type strain NJ-35, and the biofilm formation ability of Δ was remarkably decreased compared to that of the wild-type strain and complement strain was completely deficient in the promotion of the biofilm formation activity by NE, revealing that QseC was necessary for NE to regulate the biofilm formation of was strikingly increased (<0.01), but still lower than that of the wild strain NJ-35 and complement strain + caused by NE, showing that except for QseC, NE could regulate the hemolytic activity of NJ-35 through another non-QseC pathway. Furthermore, NE can dramatically increase the mortality of the wild-type strain NJ-35 against tilapia, while the deletion of the gene inhibited the enhanced-virulence by NE. However, there were no significant differences in the motility, lipase activity, or protease activity between the wild type strain and mutant △ gene inhibited the NE-stimulated growth and virulence of NJ-35, indicating that QseC could regulate the pathogenicity of by recognizing and responding to NE. It is crucial for our study to comprehensively understand the pathogenesis of and the mechanisms behind the interactions between pathogens and their hosts. This study provides the theoretical foundations for new technologies for prevention and control strategies against bacterial diseases.