When the local scour hole is formed around the pile foundation, the effective buried depth of the pile foundation will be reduced, which increases the safety hazard of the engineering structure. The scour models in the current research are mostly symmetrical, but the scour holes in engineering practice are asymmetric, which makes the pile foundation in a more unfavorable state. How to calculate the stress change of the soil caused by scour reasonably is pivotal for evaluating the bearing capacity of the pile foundation. However, there is still no strict theoretical calculation method. This paper aims to propose a simplified three-dimensional asymmetric scour hole model based on the asymmetric scour hole shape measured in the experiment. Which is based on the application of Boussinesq's equation in a semi-infinite space and regard the soil above the depth of the scour hole as a load. The calculation method of the vertical and horizontal effective stress of the soil in the asymmetric scour hole is derived. The "active and deactive element" in the finite element method is used to simulate the formation of scour holes in the semi-infinite space foundation, and the FEM results are compared with those obtained from the theoretical calculation method, which verifies the correctness of the theoretical calculation method in this study. Subsequently, based on the theoretical calculation method, the influence of the pile foundation is considered, and compared with the FEM results. The comparison results indicate that the theoretical calculation method in this research is feasible. Based on this, the sensitivity analysis of the parameters in the simplified model of the three-dimensional asymmetric scour hole was carried out, and the changes of the vertical and horizontal effective stress difference of the soil around the pile under the condition of the asymmetric scour hole were obtained.