Abstract: One of the most effective methods to reduce the gas content of coal seam is to pre-drain gas by drilling along the seam. Rational borehole layout parameters are the key to improve the effectiveness of coal seam gas pre-drainage. In order to improve the accuracy and scientificity of borehole layout in seam drilling, a fluid-solid coupling model of gas-containing coal was established. Based on the response surface method, an optimization scheme of borehole arrangement parameters was designed. The COMSOL Multi-physics simulation software was used to analyze the influence of the interaction between geological factors(coal seam gas content, gas permeability coefficient) and engineering factors(drainage negative pressure, borehole diameter, borehole spacing) on the pre-drainage of coal seam gas by drilling. The determination index of the ratio of the maximum gas pressure between boreholes to the standard pressure(P_max/P_b) was proposed. The precise distribution method for pre-draining coal seam gas by “time-sharing partition” type of boreholes was developed. The optimal borehole layout parameters suitable for different coal seam gas occurrence characteristics were obtained. Finally, the field test of gas pre-drainage was carried out. The results show that the superimposition effect of drainage between adjacent boreholes was not obvious at the initial stage of pre-drainage. As the pre-drainage time was extended, the superimposing effect of draining became more and more significant, and the drainage standard area in the vertical borehole direction gradually changed from isolated to composite. Under different pre-draining times, the sensitivity of P_max/P_b to various factors was as follows: borehole spacing > coal seam gas content > gas permeability coefficient > borehole diameter > drainage negative pressure. The interaction response contours of coal seam gas content and permeability coefficient were densely distributed, which indicated that both have a very significant effect on P_max/P_b and greater impact on the value of P_max/P_b. Among the engineering factors, the interaction response contours of negative pressure and borehole diameter were distributed in a circular shape, indicating that the interaction between the two was not obvious. Under the interaction of borehole spacing and geological factors, the response contours were denser in the borehole spacing direction, and the effect of borehole spacing on P_max/P_b was still obvious, which was mutually corroborated by the results of single factor analysis. The reasonable borehole layout parameters determined by the time-sharing district type of accurate borehole layout method in the test workface were as follows: drainage negative pressure was 24.0 kPa, borehole diameter was 113 mm, and borehole spacing was 6.0 m. After optimizing the parameters of pre-drainage borehole, the on-site gas pre-drainage effect was good and the pre-drainage compliance test was qualified, which realized the accurate pre-drainage of coal seam gas.