The present invention describes an efficient and rapid protocol to generate hepatocyte cells from human induced pluripotent stem cells (iPSCs). According to the method, the iPS cells can be differentiated into functional hepatocyte cells in a short time course (less than 15-20 days). The iPSC-derived hepatocyte cells of the invention have a similar gene expression profile to mature hepatocytes. Moreover, the iPSC-derived hepatocyte cells is proved to rescue lethal fulminant hepatic failure in a non-obese diabetic severe combined immunodeficient mouse model. The rapid and efficient differentiation protocol for generation of iPSC-derived hepatocyte cells may offer an alternative option for treatment of liver diseases.
