Up to now, available reports about the function of CD147 in IBD are limited; herein, we showed that CD147 aggravated intestinal inflammation by the activation of pyroptosis and treatment of IECs with CD147 significantly promoted IL-1β and IL-18 expression and secretion in IECs, which is attributed to the activation of caspase-1, leading to the cleavage of pro-IL-1β and IL-18 into mature IL-1β and IL-18 and their release into the extracellular microenvironment via GSDMD and GSDME. Here, GSDMD is linked to inflammatory bowel disease.