Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by co-precipitating Fe2+ and Fe3+ in an ammonia solution. SPIONs modified with [3-(2,3-epoxypropoxy)propyl] trimethoxy silane, which resulted in the presence of a high population of epoxy groups on the particles surface. The surface functional SPIONs can be bound with active bio-substance, and have a wide application prospect in the fields of biology and medicine. The binding percentage of proteins was studied with epoxy modified SPIONs. Several serum proteins including albumin, α-globulin, hemoglobin, cytochrome c and myoglobin were studied for immobilization. Epoxy terminated SPIONs were shown the highest binding ability for immobilization of cytochrome c and hemoglobin with 1 and 0.86 mg total protein at a particle concentration of 20 mg/mL among proteins, respectively. This binding ability was also shown by using sodium dodecylsulfate polyacrylamide gel electrophoresis technique (SDS-PAGE). Protein attachments were also examined by Scanning Electron Microscopy (SEM). © 2012 American Scientific Publishers. All rights reserved.