To investigate the effect of berberine (BBR) on non-alcoholic fatty liver disease (NAFLD), a cellular model of NAFLD based on HepG2 cells induced by oleic acid (OA) was used. The fat overload and triglyceride (TG) content quantities of the cellular model were documented by oil red O staining. The expression of the genes involved in lipogenesis, including farnesoid X receptor (FXR), sterol regulatory element-binding proteins-1c (SREBP-1c) and Fatty acid synthase (FAS) was assayed by real time PCR (RT-PCR) and Western-blot (WB). Results showed that BBR exerted no cytotoxicity on HepG2 cells, and BBR can significantly decrease the fat overload and TG content in OA-induced HepG2 cells. BBR increased the mRNA of FXR, but decreased the mRNA of SREBP-1c and FAS in a dosedependent manner. In addition, BBR increased the protein level of FXR but decreased the SREBP-1c and FAS. Thus BBR exerted a possible therapeutic effect on lipid metabolism disorder in the OA-induced NAFLD cellular model by regulating the FXR/SREBP-1c/FAS pathway.