GSDME is the only direct executor of caspase-dependent pyroptosis in both canonical and non-canonical inflammasomes known to date in fish, and plays an important role in anti-bacterial infection and inflammatory response. In order to determine the regulation of GSDMEa on antibacterial infection in innate immune response, the gene in common carp () was first identified and characterized, and then its function related to immune defense was investigated. Our results showed that the expressions of GSDMEa at the mRNA and protein levels were both significantly increased after intraperitoneal infection at the early stage than that in the control group. We found that GSDMEa could be cleaved by inflammatory caspase (Caspase-1b) and apoptotic caspases (Caspase-3a/b and Caspase-7a/b). Interestingly, only the GSDMEa-NT (1-252 aa) displayed bactericidal activity to and could punch holes in the membrane of HEK293T cells, whereas GSDMEa-FL (1-532 aa) and GSDMEa-CT (257-532 aa) showed no above activity and pore-forming ability. Overexpression of GSDMEa increased the secretion of IL-1β and the release of LDH, and could reduce the burdens in fish. On the contrary, knockdown of GSDMEa reduced the secretion of IL-1β and the release of LDH, and could increase the burdens in fish. Taken together, the elevated expression of GSDMEa was a positive immune response to challenge in fish. GSDMEa could perform the pore-formation in cell membrane and the regulation on the secretion of IL-lβ, and further regulate the bacterial clearance . These results suggested that GSDMEa played an important role in immune defense against and could provide a new insight into understanding the immune mechanism to resist pathogen invasion in teleost.