In the present study, we demonstrated that the co-culture of macrophages and stomach-cancer cells induced the activation of DLL3-dependent Notch1/Notch2 signaling, the upregulation of IL-33, and the degradation of the galectin-3–binding protein (LG3BP) and heat shock cognate 71 kDa protein (HSPA8), resulting in enhanced proliferation of cancer cells and elevated IL-1β, IL-12, and IL-10 secretion by macrophages. This evidence concerns the gene NOTCH1 and cancer.