To investigate the function of HOXC8 in NSCLC, we showed that knockdown of HOXC8 led to massive NSCLC cell death in a mechanism of pyroptosis because both YVAD, a caspase-1 (CASP1) inhibitor, and disulfiram, which prevents gasdermin D (GSDMD) pore formation, blocked cell death caused by HOXC8 depletion. Here, HOXC8 is linked to non-small cell lung carcinoma.