Previous studies have demonstrated the hypolipidemic activity of Moringa oleifera (MO) leaves via lowering serum levels of cholesterol, but the mechanism of action is unknown. In this study, we demonstrated the hypocholesterolemic mechanism of a phenolics-enriched extract of Moringa oleifera leaf (PMO) in HepG2 cells. When compared to the control treatment, PMO significantly decreased total intracellular cholesterol, inhibited the activity of HMG CoA reductase in a dosedependent manner and enhanced LDL receptor binding activity. Moreover, PMO also significantly increased the genetic expressions of HMG CoA reductase and LDL receptor.