To grasp the air leakage characteristics of pressure relief boreholes in deep mining and the key areas of coal spontaneous combustion prevention, combined with the actual situation of the production site, the influence range of air leakage of pressure relief boreholes was theoretically analyzed. The penetration of vertical cracks between pressure relief boreholes and roadway sides was tested by SF6 tracer method, and the air leakage rate of cracks between pressure relief boreholes was calculated, and a targeted coal spontaneous combustion prevention and control method was proposed. The results show that the pressure difference between the inside and outside of the pressure relief borehole is 11.84~20.51 Pa, which provides the driving force for the seepage and diffusion of oxygen from the roadway to the fracture zone of the borehole, and is the key factor leading to air leakage. There is a phenomenon of air leakage through the vertical cracks around and in the borehole. The direction of air leakage between the boreholes is consistent with the air flow in the roadway. The average air leakage rate on the wind side under the release point is 0.0041~0.0166 m/s. Aiming at the air leakage characteristics of pressure relief boreholes, a comprehensive coal spontaneous combustion prevention and control method is proposed, which includes “two plugging and one injection” sealing method to reduce the direct air leakage between boreholes and roadways, segmented gel injection to isolate the air leakage channel between boreholes, and roadway side grouting to block the air leakage of vertical fractures. The oxygen concentration in the borehole is maintained at 0.87%~6.71% for a long time, which effectively blocks the air leakage microcirculation and achieves the effect of coal spontaneous combustion control. This study will provide a reference for the prevention and control of coal spontaneous combustion in deep mining pressure relief boreholes.