Monitoring of drugs in vivo has been recognized as an urgent need for successful chemotherapy treatment. However, to find an appropriate tool for this purpose has been proved as a great challenge. Here, we report a PLA-PEG coated hollow X-ray and upconversion nanophosphor with folic acid as a tumor targeting ligand for a novel drug delivery system. In contrast with previously reported PLA-PEG based or PLA-PEG coated inorganic nanoparticles, our X-ray and upconversion nanophosphor based drug carriers can be used simultaneously as the drug delivery carrier and also serve as labels to track the loaded drugs (paclitaxel) by optical luminescence excited by X-ray, near-infrared light and magnetic resonance imaging. In addition, the hollow space created in our drug carriers dramatically increases the amount of loaded drug. Besides, folic acid on the surface of the drug loaded nanophosphors enhanced cellular uptake and significantly increased the drug efficacy compared with the free drug. We anticipate that these multifunctional nanocarriers will result in significant improvement and serve as a platform in the field of drug delivery.