Development of multimodal contrast agents for in vivo simultaneous multimodality imaging is an emerging interdiscipline that is paving the avenue toward the goal of personalized medicine. Herein, folic acid-conjugated silica-modified LaF3:Yb,Tm upconversion nanoparticles (UCNPs@SiO2-FA) with high La content in a single particle were strategically designed and prepared for simultaneously targeting dual-modality imaging of upconversion luminescence (UCL) and X-ray computed tomography (CT). LaF3 UCNPs were synthesized by a novel oleic acid (OA)/ionic liquid (IL) two-phase system. Afterward, a folic acid molecule was covalently anchored on the surface of UCNPs with a silane coupling agent. The UCNPs@SiO2-FA exhibits good stability, water dispersibility and solubility, low cytotoxicity, good biocompatibility, highly selective targeting, excellent X-ray attenuation, and UCL emission under excitation at 980 nm. In vivo UCL and CT images of mice show the UCNPs@SiO2-FA can be used in targeting dual-modality imaging. These results suggest that the as-prepared nanoprobe is a good candidate with excellent imaging and targeting ability for targeting dual-modality imaging of UCL and CT.