Aim To observe whether the effect of curcumin on lipid uptake of human hepatoma cell line HepG2 is related to kinesin family member 16B (KIF16B), and to explore the lipid-lowering mechanism of curcumin. Methods (1)The HepG2 cells cultured in vitro were divided into control group (curcumin concentration was 0) and 0,0, 40 μmol/L curcumin treatment groups, and CCK8 method was used to detect cell viability to determine the appropriate concentration of curcumin. (2)The HepG2 cells cultured in vitro were divided into blank control group, negative control group, rosuvastatin (positive drug) group and curcumin group. Cholesterol detection kit was used to detect the content of cholesterol in HepG2 cells; The uptake of DiI-labeled low density lipoprotein (DiI-LDL) was observed by fluorescence microscope; The protein expressions of KIF16B and low density lipoprotein receptor (LDLR) were detected by Western blot; The fluorescence co-localization of KIF16B and LDLR was observed by laser confocal microscope. Results 25 μmol/L curcumin did not affect the growth of HepG2 cells. Compared with the negative control group, the levels of total cholesterol and free cholesterol in HepG2 cells were significantly increased, the uptake of DiI-LDL by cells was significantly increased, the expressions of KIF16B and LDLR proteins in the cells were significantly increased, and the fluorescence co-localization of KIF16B and LDLR proteins in the cells was significantly increased in the curcumin group (P＜0.05). Conclusion The increase of LDL lipid uptake and LDLR expression caused by curcumin acting on HepG2 cells is related to the interaction between KIF16B and LDLR.