A series of amphiphilic graft copolymers P(HFMA)-g-P(SPEG) comprising poly(hexafluorobutyl methacrylate) (PHFMA) backbones and poly(ethylene glycol) (PEG) side chains were synthesized by copolymerization of HFMA and SPEG macromonomer with the p-vinylbenzyl end group. The SPEG macromonomer was synthesized by reacting Methoxy poly(ethylene glycol) (MPEG) with p-chloromethylstyrene in THF in the presence of NaH. The macromonomer and amphiphilic graft copolymer were characterized by FTIR, H-1 NMR, F-19 NMR, and gel permeation chromatography (GPC). The critical micelle concentration (CMC) of the amphiphilic graft copolymer was measured by surface tension technique. The results showed that the CMC decreased with increasing HFMA contents in the graft copolymers. The interaction between P(HFMA)-g-P(SPEG) and bovine serum albumin (BSA) was studied by fluorescence spectroscopy, transmission electron microscopy (TEM), and photon correlation spectroscopy (PCS). The fluorescence spectrum showed that the fluorescence intensity of BSA increased with increasing content of HFMA in P(HFMA)-g-P(SPEG) and concentration of P(HFMA)-g-P(SPEG) in the P(HFMA)-g-P(SPEG)/BSA solution. TEM micrographs showed that P(HFMA)-g-P(SPEG) mainly formed core-shell structure micelles. When BSA was added, the micelles changed from a core-shell structure into a worm-like, vesicle-like and hollow-like structure with different initial concentrations of the copolymer. The size distribution of the micelles increased proving that the copolymer micelles encapsulated the bovine serum albumin. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4895-4907, 2009