There is a very thick water-bearing key strata above the coal seam in the Binchang mining area. When the mining scale is large, it easily breaks and leads to rockburst with a surge of water gushing in the panel. Adopting the layout pattern of a small panel and a large coal pillar can improve the stability of the main key strata, but at present, the research on the layout pattern of a small panel and a large coal pillar under extra-thick water-bearing key strata is still not perfect. Therefore, taking the second and third panels of a mine in Binchang as the engineering background, the width of the coal pillar and the mining scale of the panel are optimized by means of theoretical analysis, field measurement, and numerical simulation to prevent rockburst and control water inflow. The results show: (1) through theoretical calculation, it is deduced that the critical width of instability of the isolated coal pillar in the current mining scale is 257 m, and the critical mining scale of breaking and instability of the main key strata in the third panel is 537 m; (2) considering the bearing capacity of the isolated coal pillar and the recovery rate of coal resources, the reasonable width of the isolated coal pillar is 210~270 m, and when the width is 200 m and 250 m, the reasonable mining scale of the third panel is 490~550 m and 640~700 m, respectively; (3) the field practice shows that the actual width of the coal pillar between the second and third panels is less than the reasonable width, and the stress concentration in the isolated coal pillar area is relatively high, so the roof deep hole blasting and large-diameter drilling in coal seam are adopted to relieve pressure. After taking pressure relief measures, the stress concentration in the isolated coal pillar area is effectively reduced, and the pressure relief effect is remarkable.