G-protein-coupled receptor 120 (GPR120) plays an important role in regulating lipid and glucose metabolism as a long-chain unsaturated fatty acid receptor. However, it has been widely accepted that omega-3 polyunsaturated fatty acids are not dependent on the activation of GPR120 to exert anti-tumor activity. Therefore, the role of GPR120 in tumor development has not yet been elucidated. Here we show that activation of GPR120 promotes angiogenesis and metastasis in human breast cancer. We show that activation of GPR120 in human breast cancer cells can promote vascular endothelial growth factor, interleukin-8 secretion, cell migration, and epithelial mesenchymal transition. Similarly, phosphatidylinositide 3-kinases/RAC-alpha serine/threonine-protein kinase/nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway is involved in GPR120 activation-induced cell migration and epithelial mesenchymal transition in breast cancer cells. In conclusion, our findings indicate that GPR120 acts as a cancer-promoting receptor in the development of breast cancer. Therefore, GPR120 is expected to be a potential new target for cancer therapy.