Protein-based nanoparticles represent a promising approach to carry polypeptide and protein drugs. Using both theory and experimentation, an interferon α-1b (IFN) delivery system carried by bovine serum albumin (BSA) nanoparticles was designed. Theoretical results indicate the most probable binding site and interaction mechanism for IFN on BSA. IFN has a higher binding affinity with BSA compared with small chemical drugs. The drug loading is about 8 mg/g, significantly higher than those reported in other literature. The release profiles differ between the nanoparticles prepared by the incorporation method and the adsorption method. The adsorption of IFN on BSA nanoparticles is monolayer adsorption. The fact that IFN was carried successfully by BSA nanoparticles establishes a solid basis for expanding the drug loading field of BSA nanoparticles to proteins and polypeptides.