Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis. Xanthohumol (XN) is a prenylatedchalcone derived from hops (Humuluslupulus L.) that decreases atherosclerotic lesion area. However, the underlying molecular mechanism of the anti-atherosclerosis effects of XN is still unclear. Therefore, in the present study, we investigated the effects of XN on human aortic smooth muscle cells (HASMCs) proliferation and migration, the potential mechanism was also explored. Our results showed that XN significantly inhibited platelet-derived growth factor-BB (PDGF-BB)-induced HASMC proliferation and migration. It also induced the arrest of cell cycle progression at G0/G1 phase. In addition, XN significantly inhibited the phosphorylation of PDGF receptor (PDGF-R) beta, AKT and ERK1/2 in PDGF-BB-stimulated HASMC. In conclusion, this study demonstrated that XN inhibits PDGF-BB-induced HASMC proliferation and migration through suppression of PDGF signaling pathway. Therefore, XN may be a potential candidate for preventing or treating atherosclerosis.