In this pan-cancer study, we found that (1) genome of GSDM genes were extensively altered in cancer and the corresponding patients showed survival disadvantage; (2) the expression of GSDM genes was altered in cancer due to genetic alteration and epigenetic modification of GSDM genome, and it affected patient survival; (3) GSDM family members were involved in cancer-related pathways in varying degrees and had a role in drug sensitivity; (4) the expression of GSDM genes associated with immune subtypes, TME and cell stemness of cancer. The gene discussed is GSDMA; the disease is cancer.