Aim To investigate the effect of oxidized low-density lipoprotein (ox-LDL) on the synthesis of hyaluronic acid (HA) in human aortic vascular smooth muscle cells (HAVSMC), and explore its molecular mechanism. Methods The T/G HAVSMC were cultured in vitro with different concentration of ox-LDL(0,5, 0,5, 100 mg/L), the CCK-8 method was used to measure the cell proliferation and grouping analysis was carried out. T/G HAVSMC were treated with ox-LDL at concentrations of 25 and 50 mg/L for 48 hours. Natural LDL (N-LDL) group (50 mg/L N-LDL) and control group were set up. HPLC was used to determine the HA content, real-time quantitative PCR was used to detect the mRNA level of hyaluronic acid synthetase 2 (HAS2) and hyaluronic acid synthase 3 (HAS3), Western blot was used to detect the protein level of lectin-like oxidized low density lipoprotein recepter-1 (LOX-1), low-density lipoprotein receptor-related protein-1 (LRP), scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) and cluster of differentiation 36 (CD36). Results After 48 h intervention, ox-LDL had no significant cytotoxicity on T/G HAVSMC cells. After 25 and 50 mg/L ox-LDL intervention for 48 h, the content of HA were significantly higher than those in the N-LDL group and the control group(P<0.05), the mRNA expression levels of HAS2 and HAS3 were significantly higher than those in the N-LDL group and the control group(P<0.05), and there was no significant difference between the N-LDL group and the control group(P>0.05). The expression of LOX-1 in 25 mg/L ox-LDL group and 50 mg/L ox-LDL group was significantly higher than that in the N-LDL group and the control group(P<0.05), while the expression of LRP-1, SR-PSOX and CD36 showed no significant change(P>0.05). Conclusion ox-LDL could induce the synthesis of HA in human aortic smooth muscle cells, and its mechanism may be related to the combination of LOX-1.