Aim To explore the effect of Curcumin on that inducible degrader of the low density lipoprotein receptor (IDOL) regulating the uptake of low density lipoprotein cholesterol (LDLC) of hepatocytes. Methods HepG2 and LO2 cells (two kinds of hepatocytes) were infected with the constructed overexpression or RNA-interference IDOL (OE/RNAi-IDOL) lentivirus. The efficiency of the lentiviral infection experiment was evaluated by fluorescence microscopy. The expression of IDOL and low density lipoprotein receptor (LDLR) proteins was detected by Western blot. After HepG2 and LO2 cells were treated with Curcumin for 24 hours, intracellular lipid droplets were determined by red oil O staining; cholesterol content was detected by using cholesterol testing kits; the uptake of LDLC by hepatocytes was detected by DiI-LDL uptake experiment; LDLR abundances of hepatocytes surfaces were determined by immune flow cytometry. Results Compared with white light view, the phenomenon of the green fluorescence was observed both in HepG2 and LO2 cells infected by OE-IDOL and RNAi-IDOL lentivirus; Western blot results showed that both in HepG2 and LO2 cells infected by RNAi-IDOL-2 lentivirus, IDOL protein expression were decreased, while LDLR expression was increased (P＜0.01); on the contrary, in HepG2 and LO2 cells infected by OE-IDOL lentivirus, IDOL protein expression was increased, while LDLR expression was decreased, the above results indicated that both HepG2 and LO2 cells infected by OE/RNAi-IDOL lentivirus had been acquired. Compared with the control group of HepG2 and LO2 cells without any treatment, after 25 μmol/L Curcumin treatment for 24 hours in the OE/RNAi-IDOL lentivirus infected cells, both the intracellular lipid droplet content and relative cholesterol content were increased in the treatment group (P＜0.01), meanwhile the uptake LDLC ability and cell surface LDLR abundances of hepatocytes were also enhanced (P＜0.01), the same trend was also observed in the results of Rosuvastatin treatment group. Conclusion The levels of IDOL protein in liver cells were down-regulated by Curcumin, which further promotes the uptake of LDLC of liver cells.