Poly(2-hydroxyethyl methacrylate)/3-(2-imidazoline-1-yl) propyl(triethoxysilane) (PHEMA/IMEO) nanoparticles were attached on surface plasmon resonance (SPR) sensor for the real-time detection of human immunoglobulin G (IgG) in human serum. The PHEMA/IMEO nanoparticles-attached SPR sensor was characterized by Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and contact angle measurements. IgG detection studies were performed using aqueous IgG solutions at different concentrations. In order to show the selectivity and specificity of the SPR sensor, competitive kinetic analyses were performed using IgG, albumin, hemoglobin in singular and competitive manner. Finally, IgG detection in human serum was carried out.