The amphiphilic and biocompatible behaviors of Poly (acetate-methylacrylic acid) Poly(EA-MAA) were investigated in this study. The aggregation behavior of Poly(EA-MAA) in aqueous media was investigated by steady-state fluorescence spectroscopy and surface tensiometry. The critical aggregation concentration (cac) of Poly(EA-MAA) was determined to be 0.03 mg/mL. Ultraviolet spectrum (UV) and fluorescence spectrum results indicated that there are interactions form between Poly(EA-MAA) and bovine serum albumin (BSA). And beta-sheet can be changed into a-helix of BSA in Poly(EA-MAA) solution effectively revealed by Circular dichroism (CD), which is driven by the H-bond and hydrophobic interactions. The good cell-compatibility of Poly(EA-MAA) makes it great potential in the biomedical fields. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013