Abstract: The pilot production of natural gas hydrates demonstrates that the electric submersible pump (ESP) is the most applicable tool to artificial lifting in depressurization recovery of natural gas hydrates. Based on a comprehensive analysis of multiple factors, such as the complex zonal production pipe string, the temperature field of the ambient seawater environment, ESP, and gas-liquid separator, the gas-liquid two-phase wellbore flow model was developed for ESP-assisted depressurization recovery of offshore natural gas hydrates. The heat transfer processes of different pipes were analyzed and the flow regime distribution, and temperature and pressure profiles of different pipes were predicted. Finally, the production operation was optimized using the proposed model. The results show that during depressurization recovery of natural gas hydrates, the working fluid level in the gas production pipe can be lowered by increasing the wellhead back pressure or decreasing the ESP frequency, to reduce the risks of continuous water production from gas production pipes. This research provides references for production optimization of ESP-based dewatering and gas recovery during depressurizing offshore natural gas hydrate reservoirs.