In the present study, we report that overexpression of Tob1 induces apoptosis and inhibits the proliferation, migration and invasion of gastric cancer cells, at least in part, by activating the expression of Smad4 and its target gene p15 as well as by downregulating the expression of β-catenin and its target genes, such as cyclin D1, uPAR and PPARδ. The gene discussed is SMAD4; the disease is gastric cancer.