During photodynamic therapy (PDT) of cancers, there are numerous side effects, accompanied by damage to normal cells/tissues caused by the abnormal elevation of reactive oxygen species (ROS). In this paper, we aim to provide an effective method to reduce the relevant side effects of PDT by using cerium oxide nanoparticles. The well-dispersed poly(vinyl pyrrolidone) stabilized cerium oxide nanoparticles were successfully synthesized by using a one-pot method at 60 degrees C in slightly alkaline environment. The morphological and structural characterizations clearly illustrate the excellent lattice structures of cerium oxide, nanoparticles. The MTT assay indicates that these cerium oxide nanoparticles show no intrinsic cytotoxicity even at a concentration up to 300 micro g/mL. More importantly, the results demonstrate that these nanoparticles can selectively protect human normal cells but not the cancer cells from ROS damage after exposure to UV-radiation, suggesting their potential applications for PDT treatment. The rationale behind the selective protection effect can be attributed to the hindrance of the Ce (III)/Ce (IV) redox reaction cycle on the surface of cerium oxide nanoparticles due to the abnormal intracellular pH in cancer cells. Furthermore, these cerium oxide nanoparticles can be used as effective drug carriers for enhancing drug delivery efficiency to target cancer cells like hepatoma HepG2 cells. This raises the possibility of applying cerium oxide nanoparticles for multifunctional therapeutic applications, i.e., combination of efficient PDT and chemotherapy.