The metal layer in a multilayer emitter can still be oxidized in vacuum at a high temperature over 1400 K, limiting the application of the emitter in a thermophotovoltaic system. To take a further insight into the above phenomenon, multilayer Mo/HfO2 emitters were fabricated and annealed at a temperature range of 1000∼1500 K under a constant pressure of 3×10−4 Pa. Then, the measurements of the structure morphologies, compositions and spectral emittances on the emitters before and after thermal annealing were conducted to investigate the oxygen diffusion process and its effect on the spectral emittances. Moreover, an improved model based on the transfer matrix method was proposed to predict the spectral emittance of the degraded emitter. It is indicated that the emitter can keep the efficient selective emission up to 1300 K, while it exhibits a thermal degradation at 1500 K. The main reason is that Mo is oxidized at the high temperature, and the generated oxides sublimate to form holes, resulting in significant changes in both the structure and composition of the emitter. With an analysis on these changes, it is inferred that the pinholes produced by the internal stress at the boundary between Mo and HfO2 account for the oxygen diffusion. The predicated spectral emittances after the thermal annealing show a similar trend with the measured ones, providing a further demonstration for the reason of the thermal degradation. This study gives valuable insights into the oxygen diffusion process and thermal degradation of the multilayer emitters, and it can pave the way for the design of the thermophotovoltaic emitter with a high-temperature resistance.