Gingerols including 6-gingerol, 8-gingerol and 10-gingerol are the pungent ingredients in ginger. Ginger extract and 6-gingerol have been reported to possess hypocholesterolemic activity. However, cholesterol-lowering activity of 8-gingerol and 10-gingerol has not been well investigated. The present study was to investigate effect of 8-gingerol and 10-gingerol on cholesterol level in HepG2 cells compared with 6-gingerol. HepG2 cells were incubated with 40 μM cholesterol and 4 μM 25-hydroxycholeterol with various concentrations of 6-gingerol, 8-gingerol or 10-gingerol, ranging from 0 to 100 μM for 24 h. It was found that 10-gingerol at 75 and 100 μM was more effective in decreasing cholesterol levels compared with 6-gingerol and 8-gingerol. Furthermore, 10-gingerol increased the expression of LDLR with a dose–response manner through up-regulating SREBP-2 and down-regulating PCSK9. 10-Gingerol also enhanced the expression of genes related to cholesterol efflux and bile acid expression including ABCG5/8 and ABCA1 through LXRα, PPARγ and CYP7A1 in HepG2 cells.