It has been well-established that nanomaterials provide a robust framework into which two or more functional moieties can be integrated to offer multifunctional and synergetic applications. We report here the facile synthesis and systematical investigation of the luminomagnetic core-shell nanoparticles (NPs) with the magnetic Fe3O4 core coated with a silica shell incorporating fluorescent Ru(bpy)3. The luminomagnetic NPs were monodisperse and spherical in shape with a diameter of 60±10 nm. The luminomagnetic NPs possessed not only the desirable optical signature of Ru(bpy)3(2+) but also the distinctive magnetic profile of Fe3O4, where a strong red-orange emission and the super-paramagnetic characteristics with the saturation magnetization values ca. 10 emu/g were observed for the luminomagnetic NPs. As revealed by Alamar blue assay and flow cytometry analysis, the Fe3O4 NPs decrease the cell viability of HepG2 by ca. 10%, while an increase by ca. 10% on HepG2 cell proliferation was revealed after the silica shell was coated onto Fe3O4 NPs, suggesting that the silica shell serves as a protective layer to increase the biocompatibility of the luminomagnetic NPs. Confocal laser scanning microscopy, transition electron microscopy and magnetic resonance (MR) images confirmed that the luminomagnetic NPs can enter into the interiors of HepG2 cells without damage, highlighting their capabilities for simultaneous optical fluorescence imaging and T2 MR imaging. Taking advantage of versatility of silica shell towards different surface modification protocols, the luminomagnetic NPs were successfully functionalized with epidermal growth factor receptor (EGFR) antibody for HepG2 cell recognition. All the results illustrated that the luminomagnetic NPs should be a potential candidate for future cancer diagnosis and therapy.