The 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 lung injury during sepsis. NF-κB, JAK2 / STAT3 and MAPK signaling pathways are involved in NLRP3-mediated pyroptosis. Targeting NLRP3-pyroptosis and its related signaling pathways, pharmacological interventions with Physalin B, schisandrin, erythropoietin, and physical therapies such as acupuncture at Zusanli and Feishu points, as well as NLRP3-specific inhibitors like ergolide, have all shown effective anti-septic effects in treating lung injuries. This article reviewed the roles and mechanisms of NLRP3-pyroptosis in sepsis-induced lung injury, as well as the experimental progresses made in targeting NLRP3 pyroptosis as a therapy. We aim to highlight the importance of NLRP3-pyroptosis as a target, providing insights for the prevention and treatment of sepsis-induced lung injury.