Abstract: The goaf of coal mine is a key area for the prevention and control of coal spontaneous combustion fire, the current measures to block air leakage can not completely solve the problem of spontaneous combustion in the goaf, inert composite materials and inert gases are often used to fill and inert the goaf in the prevention and control of coal spontaneous combustion fire in the goaf of coal mine. This paper briefly analyzes the fire prevention and extinguishing mechanism of inert composite materials and inert gas, and studies and analyzes the practical application effect of fly ash grouting and liquid CO2 in the prevention and control of coal spontaneous combustion fire in 22101 water gushing goaf by using optical fiber temperature measurement and bundle tube gas measurement technology. The results show that in the goaf with large water inflow, the environmental adaptability of liquid CO2 is better than that of fly ash grouting, which can quickly diffuse and inert the proposed treatment area and interrupt the accelerated oxidation process of residual coal ; Before the formation of asphyxiating environment in goaf, the oxidation process of residual coal slows down but still continues. The analysis shows that the diffusion and retention of fly ash grouting under complex regional working conditions need to be further improved. Combined with liquid CO2, it has a better effect on the prevention and control of spontaneous combustion fire in water gushing goaf.