Uniform fluorescein isothiocyanate (FITC)-incorporated silica-coated core-shell SPIO nanoparticles (MNP@SiO2) with sizes of about 30 nm have been prepared by controlled hydrolysis of tetraethyl orthosilicateb. Monoclonal antibody nimotuzumab (h-R3) is labeled to the core-shell MNP@SiO2 for targeting to cancer cell A431 overexpressing epidermal growth factor receptor (EGFR). The result shows h-R3 labeled MNP@SiO2 nanoparticle (MNP@SiO2-mAb(h_R3)) has desired specificity to cancer cell A431. Compared to BSA labeled MNP@SiO2 nanoparticle (MNP@SiO2-BSA), MNP@SiO2-mAb(h_R3) could increase the cellular uptake of endocytosis and cytotoxicity due to h-R3 binding.