Inactivation, deletion or mutation of Smad4 exists in a variety of malignant tumors, and mutation of TGF-β RII has been demonstrated in gastrointestinal cancer, hepatocellular carcinoma, and gallbladder carcinoma cells, which weaken the negative regulatory mechanism of cancer cells, leading to the development of malignant cancers [52,53]. The gene discussed is SMAD4; the disease is cancer.