Pyroptosis, an active form of cell death mediated by the gasdermin family proteins (GSDMA, GSDMB, GSDMC, GSDMD, GSDME, and DFNA5), has been increasingly recognized as a significant player in pulmonary diseases, particularly lung cancer and pneumonia. The gasdermin proteins play a crucial role in cell membrane pore formation, leading to chromatin fragmentation, cell swelling, and plasma membrane lysis. Pyroptosis is initiated by caspase-1 activation, which activates the NLRP3 inflammasome, leading to the release of inflammatory cytokines such as IL-1β and IL-18. This review highlights the multifaceted roles of pyroptosis in respiratory diseases, including its dual nature in promoting and inhibiting disease progression. In lung cancer, pyroptosis can both enhance antitumor immunity and increase adverse drug reactions. In pneumonia, pyroptosis can protect against infection but also contribute to tissue injury and host lethality. The review also discusses the potential therapeutic implications of targeting pyroptosis, emphasizing the need for precise drug delivery and a deep understanding of the molecular mechanisms to optimize treatment outcomes. Overall, the complex role of pyroptosis in respiratory diseases underscores the importance of further research to harness its therapeutic potential.Pyroptosis, an active form of cell death mediated by the gasdermin family proteins (GSDMA, GSDMB, GSDMC, GSDMD, GSDME, and DFNA5), has been increasingly recognized as a significant player in pulmonary diseases, particularly lung cancer and pneumonia. The gasdermin proteins play a crucial role in cell membrane pore formation, leading to chromatin fragmentation, cell swelling, and plasma membrane lysis. Pyroptosis is initiated by caspase-1 activation, which activates the NLRP3 inflammasome, leading to the release of inflammatory cytokines such as IL-1β and IL-18. This review highlights the multifaceted roles of pyroptosis in respiratory diseases, including its dual nature in promoting and inhibiting disease progression. In lung cancer, pyroptosis can both enhance antitumor immunity and increase adverse drug reactions. In pneumonia, pyroptosis can protect against infection but also contribute to tissue injury and host lethality. The review also discusses the potential therapeutic implications of targeting pyroptosis, emphasizing the need for precise drug delivery and a deep understanding of the molecular mechanisms to optimize treatment outcomes. Overall, the complex role of pyroptosis in respiratory diseases underscores the importance of further research to harness its therapeutic potential.