The oxidation and failure process of multilayer films of depleted uranium and gold were studied during being exposed to atmosphere. These samples which had the same thickness with the ignition hohlraum were prepared by magnetron sputtering. X-ray photoelectron spectroscopy depth profile analysis was performed to investigate the chemical compositional distribution of samples exposed for different periods. The morphologies of samples were studied with scanning electronic microscope and optical microscope in the meantime. And the failure mechanisms were discussed based on the above analysis. The results show the native defects in samples have a significant effect on the oxidation process and deterioration degree. The grain boundary of gold layer forms the fast diffusion channel for the oxidizing gases in atmosphere. The multilayer structure of samples keeps intact in this experimental period. The nodules embedded in the depleted uranium layer seriously decrease the corrosion resistance and weaken the mechanical stability of the whole sample. It causes coating damage, induces interfacial debonding between two layers, and serious oxidization of the depleted uranium layer finally. According to the results of failure analysis, the deposition process of the gold and uranium layer is improved. Finally, the multilayer film with specified shelf-life is prepare.