Lanthanide-based multimodal probes with high sensitivity, simple synthesis strategy, and good biocompatibility promise new applications for clinical diagnosis. However, today's challenge is not only to develop high-performance multimodal probes for more accurate and reliable diagnosis, but also to understand the fate of these probes in vivo. In this context, a novel PEGylated Dy-doped NaGdF4 nanoprobe (PEG-NaGdF4:Dy) was designed and fabricated as a T1/T2-weighted MRI/CT imaging agent. This nanoprobe has a distinct longitudinal relaxivity (r1 = 5.17 mM(-1) s(-1)), relatively high transverse relaxivity (r2 = 10.64 mM(-1) s(-1)), and exhibits strong X-ray attenuation properties (44.70 HU L g(-1)) in vitro. Furthermore, T1/T2-weighted MRI/CT imaging in vivo confirmed that this PEG-NaGdF4:Dy nanoprobe could lead to a significant contrast enhancement effect on liver, spleen and kidney at 24 h post injection. The MTT assay, histological analysis, and biodistribution investigation demonstrated that this multifunctional nanoprobe possessed relatively low cytotoxicity, negligible tissue damage and could be completely excreted out of the body of mice as time prolonged. Therefore, the present PEG-NaGdF4:Dy nanoprobe has the potential for the development of multifunctional T1/T2-weighted MRI/CT imaging to provide more comprehensive and accurate diagnosis information.