Zirconium oxide cluster anions ZrxOy- are prepared by laser ablation and are reacted with n-butane in a fast flow reactor under near room temperature conditions. A time-of-flight mass spectrometer is used to detect the cluster distribution before and after the reactions. Observation of a hydrogen atom pickup product Zr2O8H- indicates a C-H activation reaction: Zr2O8- + n-C4H10 -> Zr2O8H- + C4H9. Density functional theory calculations predict that the oxygen-very-rich cluster Zr2O8- contains one mononuclear oxygen-centered radical (O-center dot), which leads to a high C-H activation reactivity, in agreement with the experiments. This study provides one example for how the highly oxidative O-center dot radical may be generated by adsorption of O-2 onto unreactive metal oxide clusters.