Abstract: The variation of coal seam thickness is one of the important factors affecting the pressure relief of large-diameter drilling hole. We have established an elastic model of pressure relief of large-diameter drilling hole based on the principle of equivalent elastic modulus. Taking two working faces of a mine as engineering background, we have studied key issues of large-diameter drilling hole regarding coal seam thickness, including the stress distribution characteristics and energy release laws, and the pressure relief and energy release mechanism. Several phenomena of engineering significance have been revealed by our research. Firstly, when the parameters of large-diameter drilling hole are the same, the stress of primary rock, tangential stress and plastic zone range of thin coal seam are greater than those of thick coal seam. Secondly, the peak stress around the large-diameter drilling hole decreases nonlinearly with the increase of coal seam thickness. When the coal seam thickness increases from 1 m to 9 m, the peak stress drops by 12.9%, from 23.2 MPa to 20.2 MPa. Likewise, the pressure relief and energy release rate also decreases with the increase of coal seam thickness. When the coal seam thickness increases from 1 m to 9 m, the pressure relief and energy release rate of large-diameter drilling hole decreases from 68.7% to 45.8%, indicating that better pressure relief effect can be achieved in thin coal seam. Moreover, when the parameters of large-diameter drilling hole are the same, the increase of coal seam thickness causes decrease of the tangential stress and thereby results in the decrease of the range of coal fragmentation zone and plastic zone, and the amount of the released elastic energy, which reduces the pressure relief energy release rate. The coal seam thicknesses of working faces 1208 and 1203 of a certain mine are 9.08 m and 4.95 m, respectively. Although the same set of large-diameter drilling hole parameters is adopted for these two working faces, the one with thicker coal seam suffers from more serious surrounding rock deformation and failure. By optimizing the parameters of large-diameter drilling hole based on our research, the average amount of drilling cuttings decreased from 2.48 kg/m to 1.76 kg/m. Therefore, we suggest that as the coal seam thickness increases, measures such as reducing drilling spacing and increasing drilling diameter should be considered in order to guarantee the expected pressure relief effect.