FPH1 is a potent and selective small molecule that induced Functional Proliferation of primary human Hepatocytes in vitro, identified by a high-throughput, cell-based screening using primary human hepatocytes. It induced a significant increase in hepatocyte number and elevated the number of hepatocytes undergoing mitosis in a dose-dependent manner. Cells treated with FPH1 also maintained their liver-specific functions. Immunofluorescence staining for Ki67 and albumin, along with FACS-based cell counting, revealed that hepatocytes from a wide range of genetically diverse individuals could be expanded and normal hepatocytes functions could be maintained after expansion. FPH1 can also promote the differentiation of iPS cells toward a hepatic lineage and promote the maturation of induced hepatic cells toward a more adult-like liver phenotype.