An investigation on the influence of chemical compositions and surface properties (e.g., surface free energy in air and hydrogel-water interfacial energy) on the adsorption of bovine serum albumin (BSA) at pH 7.4 on to a series of poly(acrylonitrile-acrylamide-acrylic acid) hydrogels was carried out. The interfacial energetics were determined from the contact angle data for air-gel and octane-gel in the water environment and the specific adsorption of BSA was determined with UV-VIS spectroscopy. It is shown that the higher contents of amide and acid groups in hydrogel bulk lead to the greater polar component of surface energy in air and the greater BSA adsorption in aqueous solutions. The BSA adsorption decreases with water amount in gels at lower amide/acid contents and increases at higher contents. The results imply that the interfacial interactions between the protein and the reorganized hydrogel interface in exposure with water, as well as the penetration of protein into pores of swollen gels, influence the BSA adsorption.