In deep mines, a reasonable design of the widths of isolated coal pillars (ICPs) is critically important, particularly for hard-strata mines. This is because the frequent occurrence of mine seismicity (MS) and rockburst in deep mines often arises from the inappropriate widths of the remnant ICPs. To address this problem, this paper takes the ICP of Yingpanhao Coal Mine in Inner Mongolia in China as the engineering case study and then presents a mechanical model to illuminate the occurrence mechanism of MS induced by the mining on both sides of ICPs. The results indicate that, after the mining on both sides of ICPs, the ICPs will produce a vertical compressive deformation, and the overlying high main key stratum (MKS) will experience a flexure deformation. When the limited deflection of MKS is less than the compression of ICPs, the MKS will be fractured, and the released energy may lead to MS. Based on the mechanism model, a design criterion is proposed for ICP widths; this criterion can effectively reduce the risk of the induced rockburst and MS. Then the occurrence mechanism of MS and the design basis for ICP width are verified by numerical simulation and field microseismic monitoring. The results in this paper may be used as a theoretical guidance for rational ICP design in deep mines and may help mitigate the risk of rockburst and MS from early mining stages.