Objective To explore the influence and mechanism of stilbene glycoside on cholesterol content in HepG2 cells. Methods The cells were randomly divided into six groups: normal group, model group (ox-LDL50 mg/L) and two styrene glycoside group A (ox-LDL50 mg/L+250μmol/L), group B (ox-LDL50 mg/L+188μmol/L), group C (ox- LDL50 mg/L+125μmol/L), group D (ox-LDL50 mg/L+62.5μmol/L). After 48 h treatment, the cholesterol content of each group was observed by oil red staining and determined by cholesterol test kit, and the expression levels of ABCG1, ABCA1 and SR-BI genes in HepG2 cells of liver cancer were detected by RT-PCR technology. Results The intracellular total cholesterol (TC) and intracellular free cholesterol (FC) contents in normal group, A, B, C and D groups were lower than those in model group (P < 0.05), while the supernatant TC and FC contents in A, B, C and D groups were higher than those in normal group (P < 0.05). Stilbene glycoside can reduce the cholesterol content in HepG2 cells and increase the cholesterol outflow rate (P < 0.05), and the highest concentration of stilbene glycoside is 125 mmol/L. The expression of ABCA1 in model group was lower than that in normal group (P < 0.05). The expression levels of ABCA1, ABCG1 and SR-BI in group A, B, C and D were higher than those in model group (P < 0.05). Conclusions Stilbene glycoside can reduce the cholesterol content of HepG2 cells, and its mechanism may be increase the cholesterol outflow by up-regulate the expression levels of ABCA1, ABCG1 and SR-BI.