Hepatic tissue engineering offers a promising approach toward alleviating the need for donor liver, yet many challenges must be overcome including choice of scaffold, cell source, and immunologic barriers. Poly(lactic-co-glycolic acid) (PLGA) polymers are innovative biodegradable materials that have been shown to be useful as scaffolds for seeding and culturing various types of cells. In this study, a porous sponge scaffold of modified PLGA polymer with collagen was investigated for its ability to improve the growth and metabolism of human hepatocytes. We evaluated the biocompatibility of collagen-modified PLGA (C-PLGA) scaffolds with hepatocytes isolated from human liver. Cell adhesion and function (cell density, culture lifespan, albumin synthesis, urea synthesis, and ammonia elimination and diazepam clearance) were assessed during different culture periods. The number of hepatocytes cultured in C-PLGA scaffolds was higher compared with those cultured in PLGA scaffolds without collagen modification, and the lifespan of hepatocytes cultured in C-PLGA scaffolds was longer than that of cells cultured in PLGA scaffolds. Albumin and urea synthesis and ammonia elimination from attached hepatocytes were greater in C-PLGA than in PLGA scaffolds, with the exception of diazepam clearance. Collagen-modified PLGA scaffold is a promising biomaterial for hepatic tissue engineering.