The stress sensitivity of 15# coal seam in western Guizhou Songhe mining area was tested, the permeability of coal reservoir was studied with the effective stress, and the control of coal bed methane drainage in this area was provided. The results show that: the 15# coal seam in Songhe mining area is a strong stress sensitive coal seam, with the increase of effective stress, the permeability and stress sensitivity coefficient of coal reservoir are decreased in the form of power function, and the rate of permeability change is increased in the form of power function; when the effective stress of 15# coal seam is greater than 8 MPa, the permeability of coal seam gradually tends to be stable, the effective stress is less than 8 MPa, and the stress sensitivity of coal reservoir is stronger; in the initial stage of overlaying pressure, it is necessary to control the speed of flow pressure, give priority to water production, inhibit gas production, expand the water production radius of coal reservoirs, and avoid the damage caused by low permeability of coal reservoirs in the initial stage of gas production. For the reservoir with strong stress sensitivity, after the stress sensitive transition pressure, the flow pressure should be reasonably controlled and the stress sensitive damage should be reduced.