Nod-like receptor pyrin domain-associated protein 3 (NLRP3) -mediated pyroptosis of pulmonary parenchymal and immune cells plays a key role in the pathogenesis of acute lung injury (ALI) during sepsis, and NF-?B, JAK2/STAT3, MAPK signaling pathways are involved in NLRP3-mediated pyroptosis. Targeting NLRP3-pyroptosis and its related signaling pathway, the pharmacological intervention of Physalin B, Schisandrin, 4-hydroxynonenal, Baicalin, GYY4137, and Erythropoietin, the physiatrics of acupuncture at Zusanli and Feishu, and the NLRP3 specific inhibitors such as Ergolide, play a good anti-septic effect on ALI. This article reviews the role and mechanism of NLRP3-pyroptosis in sepsis-induced ALI, as well as the experimental progress of targeting NLRP3-pyroptosis in the prevention and treatment of sepsis-induced ALI, hoping to take NLRP3-pyroptosis as the entry point to provide thinking for the formation of a new prevention and treatment strategy for sepsis-induced ALI.