Nowadays, in order to improve the diagnostic accuracy of the disease, more and more contrast agents have been applied in the clinical imaging modalities. A combination of nanotechnology with optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI) has great potential to improve disease diagnosis and therapy. Herein, we developed a novel multimodal contrast agent for deep-tissue bioimaging based on PEGylated Mn doped NaLuF:Yb/Er nanoparticles (PEG-UCNPs). The multimodal nanoprobes have revealed the intensely red upconversion luminescence emission for deep-tissue upconversion luminescence (UCL) imaging. Moreover, Owing to the high longitudinal relaxivity, the PEG-UCNPs can be used as T-weighted MRI contrast agents. Additionally, with the high X-ray mass absorption coefficient of Lu, the novel nanoprobes are appropriate for CT imaging. With integration the high paramagnetic property, superior X-ray mass absorption coefficient and excellent upconversion luminescence in one system, the multimodal nanoprobes can provide a unique opportunity for MRI, CT and UCL imaging. More importantly, modification with PEG endows the novel nanoprobes with high biocompatibility, which would bring more opportunities for the biomedical applications in clinic.