Response surface methodology (RSM) was used to study the nitric acid leaching process of waste Co Mo based hydrotreating catalyst. The aim of this study was to introduce the CO and Mo from the spent catalyst into the solvent in the form of water-soluble, so as to facilitate the subsequent purification and recovery, and realize the harmless treatment and resource utilization of solid waste, Reaction temperature and solid-liquid ratio. The main influencing factors were determined by response surface methodology, and the model equation of process parameters and cobalt and molybdenum leaching rate was established. Under the optimal process conditions obtained by the model, the cobalt leaching rate was more than 96%, and the molybdenum leaching rate was more than 97%. It showed that the optimal process parameters obtained by response surface method were accurate and reliable, and could be used to guide the actual production process