Amphiphilic globular protein-polymer hybrids, consisting of poly(methyl methacrylate) (PMMA) as hydrophobic tail and globular protein as hydrophilic head, are prepared by the end-functional PMMA covalently binding to the primary amino groups of bovine serum albumin (BSA) in the phosphate buffer saline (PBS)/acetone mixture solvents at pH 5. The self-assembly behaviors of amphiphilic BSA-PMMA hybrids are explored in aqueous solution by the dynamic light scatter (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The self-assembled morphologies of the amphiphilic BSA-PMMA hybrids are controlled by the length of hydrophobic PMMA chains. The amphiphilic BSA-PMMA hybrids with the longer hydrophobic PMMA chains self-assembled into spherical vesicles and elongated tubular vesicles, and conversely, they self-assembled into micelles. A vesicle consists of BSA as two outer hydrophilic layers and PMMA as hydrophobic wall.