Abstract: The water, fire and explosion prevention isolation gates were the last resort of controlling major mine disasters range, so it was critical to set the location of isolation gates and investigate the safety hazards. Taking the east wing panel area of Gaohe Energy as an example, by using mine ventilation network solution, it simulated the distribution status of mine air volume and mine ventilation conditions after setting isolation gates. The isolation gates setting program was optimized. The safety hazards of mine ventilation network and the main fan were analyzed and investigated after the opening of the isolation gates. It proposed the elimination methods of mine safety hazards after the opening of the isolation gates, and provided the methods of the reasonable settings of water, fire and explosion isolation gates and safety hazards investigation for other mines.