Aim To explore the effects of momordicin-28 on cholesterol efflux and expression of related genes in Caco-2 cell,and to illuminate the role of momordicin-28 in lowering cholesterol.Methods Caco-2 cells were divided into four groups:Caco-2 cell group (control group),Caco-2 cell model group (treat cell with cholesterol),Caco-2 cell model and momordicin-28 group (treat cell with cholesterol and momordicin-28) and Caco-2+ momordicin-28 group (treat cell with momordicin-28).TC was measured by HPLC.Gene and protein expression was analyzed by semi-quantitative RT-PCR and Western blotting,respectively.Results HPLC illustrated TC was lower in momordicin-28 treat group (P<0.05 or P<0.01).Oil red staining illustrated lipidoses of Caco-2 cell were higher in the model group than that in the momordicin-28 treat group.The expression of ABCG5 and ABCG8 mRNA and protein of momordicin-28 treat group were higher than other groups (P<0.05 or P<0.01).Conclusion Momordicin-28 can facilitate efflux of cholesterol from Caco-2 cell and up-regulate expression of ABCG5 and ABCG8 in Caco-2 cell.