Abstract: It is easy to occur the complex situation in the formation of pressure depletion, such as the leakage of the well, the collapse of the well, etc. The main reason is that the stress and rock characteristic parameter will both be changed. So if the initial drilling safety mud density window is used, the choice of the density of the mud will be not reasonable, the probability of borehole problems will increase. In order to solve the above problems, on the basis of considering the influence of the change of rock characteristic parameters on the ground stress, a new calculation model of ground stress is established by assuming the formation rock is the transversally isotropic elastic material. Taking the DF111 adjusting well of DF gas field as an example, the influencing factors of ground stress are analyzed.The results show that the increase of the elastic modulus of rock will lead to the increase of the horizontal ground stress difference, and its influence on the minimum horizontal main ground stress will increase with the increase of the well depth. The change of Poisson’s ratio will not result in the change of horizontal stress difference. The reservoir pressure of DF111 adjusted well collapsed from 1.03 g/cm³ to 0.46 g/cm³, and the minimum horizontal main stress decreased by 20.5% and the maximum horizontal main stress decreased by 16.1%. The main reason for formation leakage is that the reduction of ground stress leads to the increase of effective shear stress of rock. It provides theoretical guidance for drilling in pressure-depleted formations.