Compared to the extensive studies of intestinal injury, mechanisms of NEC-induced acute brain inflammation and long-term cognitive dysfunction remain far from elucidation; here for the first time we proved that NLRP3 inflammasome activation also participated in the pathogenesis of NEC-associated brain injury, as evidenced by the increased expression of NLRP3 in hippocampus and cerebral cortex regions as well as elevated cleaved caspase-1 and mature IL-1β levels in brain tissue of NEC animals. Here, CASP1 is linked to necrotizing enterocolitis.