As prospective alternatives for natural enzymes, catalytically active nanomaterials, known as “nanozymes” have attracted considerable interest over the past decade. In this research, cerium oxide nanoparticles (CeO2 NPs) were synthesized using precursor Ce(NO3)3.6H2O by hydrothermal method. The morphology of the nanoparticles was investigated with scanning electron microscopy. The excellent catalytic response of CeO2 NPs in oxidation of 3,3',5,5'-tetramethyl benzidine (TMB) in the presence of H2O2 was obtained by taking the UV-vis spectra of the reaction solution after adding the nanoparticles. The superior peroxidase catalytic activity of CeO2 NPs can be related to increase of oxygen defects in the NPs surface through fluctuation in the atomic number between Ce3+ and Ce4+ neighbors and interatomic distances.