The integrated surface-groundwater model based on physical processes can comprehensively and systematically describe the water cycle process of the basin and provide detailed information for water resources management. At the same time, the future trends of water resources are significantly affected by climate change, and the problem as to how water resources change in future climate scenarios will affect water management measures. The authors evaluated the regional water resources response to climate change, based on the surface water-groundwater coupling model GSFLOW. By predicting the regional water resources change trend under the future climate scenario (CMIP5), the results can provide reference of water resources management for the arid regions. Some conclusions have been reached:(1) The GSFLOW model can simulate the complex water cycle of the middle reaches of the Heihe River. (2) Under the medium stabilization scenario (RCP4.5), precipitation in the region increases by an average of 0.6 mm per year, with an average temperature increase of 0.03 degrees Celsius per year, surface water flow of an average of 1.5 billion cubic meters per year, and groundwater reserves decreasing by an average of 38 million cubic meters per year. Under the high radioactive forcing scenario (RCP8.5), the average precipitation increases by 0.8 mm per year, the average temperature increases by 0.06 degrees Celsius per year, the surface water flow is 1.37 billion cubic meters per year, and the groundwater reserves decrease by an average of 34 million cubic meters per year.