Cover Story：Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for the atherosclerotic cardiovascular disease (ASCVD). Over 70% of circulating LDL-C is metabolized by binding hepatic LDL receptor (LDLR). Therefore, elevation of LDLR expression would reduce the progression of ASVCD. In order to study the molecular mechanism of Curcumin Nieotinate (CurTn) reducing lipid deposition of arterial intima by lowering plasma LDL-C, HepG2 cells were treated with 5, 10, 15 μmol/L CurTn co-incubated with 25 mg/L LDL for 24 h. Cellular lipid was detected by oil red O staining. Cholesterol content was detected by cholesterol quantitative fluorometric kit. LDL uptake was visualized by DiI-LDL and Hoechst33342. The mRNA expression of LDLR and SREBP2 was analyzed by quantitative Real-time PCR (RT-Q-PCR) and protein expression of LDLR, SREBP2 and PCSK9 by Western blotting. Oil Red O staining showed that lipid droplets increased significantly in 10, 15 μmol/L CurTn groups. The content of Cholesterol and DiI-LDL uptake were higher in 10, 15 μmol/L CurTn groups than in control group. RT-Q-PCR and Western blotting showed that CurTn increased LDLR protein expression and decreased PCSK9 protein expression, although CurTn also increased SREBP2 mRNA expression. CurTn had no effect on LDLR mRNA expression in HepG2 cells. These results suggest that PCSK9/LDLR pathway may play a key role in lowering serum LDL-C and attenuating ASCVD risk by CurTn.