We found that SCGB3A2-delivered cytosolic LPS activates non-canonical inflammasome pathway in human cancer cells when they have high expression of membranous SDC1/HS and CASP4, leading to pyroptotic death; five NSCLC and two colon cancer cells were susceptible to SCGB3A2 + LPS treatment in vitro and in vivo, resulting in growth suppression of cancer cells. Here, SCGB3A2 is linked to colonic neoplasm.