IBV is a key pathogenic agent in poultry, causing significant respiratory and renal diseases. This study investigated NLRP3 inflammasome and pyroptosis involvement in IBV-infected chicken macrophage HD11 cells. IBV infection triggered a time-dependent increase in the release of IL-1β/IL-18, along with the upregulation of inflammasome-related genes. MCC950 treatment, an NLRP3 inhibitor, notably decreased inflammatory markers while enhancing viral replication, highlighting the NLRP3 inflammasome’s function in restricting viral proliferation and mediating immunopathology. Experiments with UV-inactivated IBV demonstrated that active viral replication was essential for inflammasome activation. Pyroptosis was confirmed in IBV-infected HD11 cells through increased LDH release, characteristic ultrastructural damage, and upregulation of pyroptosis-related genes. Additionally, transfection with the IBV nucleocapsid (N) gene alone induced inflammasome activation and pyroptosis, indicating that the N protein is a key viral factor in this process. Our study offers a new understanding of IBV pathogenesis mechanisms and indicates that targeting the NLRP3 inflammasome may serve as a therapeutic approach.