〔Abstract〕 ObjectiveTo explore the inhibitory effect and related molecular mechanisms of Saponin of Schizocapsa plantaginea HanceⅠ (SSPHⅠ) on human nasopharyngeal carcinoma HONE-1 cells. MethodsThe effect of SSPHⅠ on HONE-1 cell viability was detected using the CCK-8 assay. Its inhibitory effect on cell proliferation was evaluated through a colony formation assay. Changes in cell invasion ability were analyzed using the Transwell assay. Intracellular reactive oxygen species (ROS) levels were measured using the DHE fluorescent probe. The extent of intracellular content release was reflected by the LDH release assay. The rate of cell pyroptosis was detected using the Annexin-V/PI double staining method. Changes in the expression of proteins related to the classical pyroptosis pathway were examined by Western Blot. ResultsSSPHⅠ significantly inhibited the proliferation of HONE-1 cells, increased intracellular ROS levels, and upregulated the protein expression of cleaved-Caspase-1 and GSDMD-N-terminal in a dose-dependent manner. It also promoted the release of inflammatory factors such as IL-1β, thereby inducing typical pyroptosis in HONE-1 cells. Conclusion SSPHⅠ can induce pyroptosis in nasopharyngeal carcinoma HONE-1 cells by regulating the ROS/NLRP3/Caspase-1 signaling axis, thereby exerting an anti-nasopharyngeal carcinoma effect. This suggests that SSPHⅠ may serve as a potential therapeutic agent for nasopharyngeal carcinoma.