Oncostatin M (OSM) serves as a critical maturation factor during the definitive endoderm-to-hepatocyte differentiation of human iPSCs/ESCs. Applied at the hepatoblast-to-hepatocyte transition stage—typically together with HGF and dexamethasone—OSM activates the gp130/LIFRβ receptor complex and downstream JAK/STAT3 and MAPK pathways. This drives robust upregulation of mature hepatic markers including ALB, major CYP enzymes (e.g., CYP3A4, CYP1A2), and bile acid transporters, thereby conferring drug-metabolizing, albumin-secreting, and detoxification capacities essential for functional hepatocyte-like cells and liver organoid models.