Background & Aims: Growth hormone (GH) hepatic function is mediated through multiple endocrine pathways. GH also transcriptionally activates HNF-6 (OC-1), a liver-enriched transcription factor which regulates the expression of genes essential to hepatic function. We hypothesize that GH modulates hepatic function in the normal and injured liver through HNF-6 and HNF-6 target genes. Methods: CD1 mice received PBS or GH for the 1, 7, and 28 days course of sham operation or bile duct ligation (BDL). Proliferation-, metabolic- and profibrotic-specific hepatic functions were assessed with a focus on candidate HNF-6 transcriptional target genes. Confirmation of HNF-6 regulation was done by analysis of target gene expression in liver infected with recombinant adenovirus AdHNF-6 expression vectors. Results: GH administration upregulated HNF-6 expression throughout the course of liver injury. This was associated with increased expression of HNF-6 proliferative target genes Cyclin D1, metabolic gene Cyp7A1 and downregulation of profibrogenic TGFb2R. Hepatic function improved such enhanced hepatocyte proliferation, improved cholesterol clearance throughout the course of injury and attenuated fibrogenic response at day 28 of BDL. GH treatment also transcriptionally increased Albumin expression in an HNF-6-independent manner. This was associated with enhanced serum albumin levels. Conclusions: The GH/HNF-6 axis is a potential in vivo mechanism underlying GH diverse function in the liver to modulate the liver repair response to BDL.