Aim To study the effects of high mobility group box-1 protein (HMGB1) and its receptor on proliferation and migration of human aortic vascular smooth muscle cells (VSMC) in vitro. Methods VSMC was cultured in vitro and treated with 0,0, 200 μg/L HMGB1 for 24 hours. Proliferation of VSMC was analyzed by CCK kit. VSMC migration was detected by scratch assay and Transwell chamber experiment. Real-time PCR and Western blot were used to examine receptor for advanced glycosylation end product(RAGE)expression after transfection with siRNA-RAGE. The expression of nuclear factor-κB (NF-κB) was analyzed by Western blot. Results HMGB1 could obviously promote cell proliferation and migration of VSMC (P＜0.05). Real-time PCR and Western blot assay both displayed that expressions of RAGE mRNA and protein were significantly decreased in VSMC after transfection of siRNA-RAGE (P＜0.05). Compared with HMGB1 group, siRNA-RAGE inhibited HMGB1 induced cell proliferation, migration and NF-κB protein expression (P＜0.05). Conclusions HMGB1 can promote the proliferation and migration of VSMC. The mechanism may be related to the activation of NF-κB expression after the combination of HMGB1 and RAGE.