The skin of the halibut (Reinhararditus hippoglossoides) has long been discarded as a waste product by the food industry in large quantities; hence, we examined the biological activity in the skin for utilization of the waste. In the present study, we determined induction of hepatocyte nuclear factor 3γ (HNF3γ), which is involved in liver function, using human hepatoma cell line HepG2 and extracellular matrix components extracted from the fish skin. Induction of the HNF3γ was detected by reporter plasmid constructed with the promoter region of the HNF3γ gene and luciferase or green fluorescent protein genes. The alkali extract containing proteoglycan showed HNF3γ induction, but the acid-extract enriched in collagen did not. Consequently, dermatan sulfate showed the strongest activity in HNF3γ induction. These observations suggested that fish skin has some significant biological activity, and indicates its possible function in the food and drug industry