Guide Basin is a potential site for enhanced geothermal system development in China. The optimal strategy is needed to maximize heat production potential and provide support for the future stimulation design. In this work, sensitivity analysis of influence factors on water flow path, production water temperature, and flow impedance is performed on the basis of hydraulic-thermal model of Guide Basin. The factors include reservoir parameters (length, width, height, permeability, and temperature) and operation parameters (injection rate, injection temperature, open hole length, and height difference of open hole). Results indicate that the main affecting factors of water flow path are stimulated reservoir permeability and injection rate. The most significant influencing factor of flow impedance is stimulated reservoir permeability. Reservoir geometry has the greatest influence on production water temperature. The stable period of production water temperature is mainly affected by reservoir geometry and the height difference of open hole. In the theoretically optimal strategy, the electrical powers of 150, 400, and 450 kg/s are 12.3, 32.7-33.3, and 36.2-37.6 MW, respectively. In the practically optimal strategy, the maximum injection rate is 80 kg/s and electrical power ranges from 0 to 1.25 MW. For future applications, the shallow reservoirs with high temperature are expected. (C) 2020 Elsevier Ltd. All rights reserved.