Self-aggregation and the hemolytic effect limit the application of gamma-cyclodextrin (gamma-CD) in bioactive molecular delivery systems. In this study, gamma-CD was modified by grafting onto bovine serum albumin protein (BSA), with epichlorohydrin (ECH) acting as the cross-linking agent. The effects of BSA concentration, reaction temperature, pH and time on the grafting rate were studied, and the gamma-CD-BSA complex with a grafting rate of 99.5 +/- 0.1% +/- 0.06)% was achieved. The complex was confirmed using H-1 NMR and FT-IR spectra. Compared with gamma-CD, the hemolytic effect and self-aggregation of gamma-CD-BSA were significantly reduced, and the encapsulation efficiency of curcumin was increased by 10.8%. The results of scanning electron microscopy showed that both gamma-CD and gamma-CDBSA nanoparticles were formed and the structure of the gamma-CD-BSA complex was more uniform. The pH stability and salt stability of gamma-CD-BSA were higher than gamma-CD. The release rate of gamma-CD-BSA was 15.2 +/- 0.2% after 2 h at pH 1.2, and 57 +/- 1% after 4 h at pH 7.2. The gamma-CD-BSA nanoparticles could protect curcumin in acidic environments and release it in neutral environments. The results suggested a promising wall material for delivery of hydrophobic substances.