The mechanical microenvironment of the callus plays an important role in fracture healing. Many literatures have studied the influence of parameters in the mechanical microenvironment (such as fixator configuration, loading, etc.) on fracture healing. Few of them consider the influence from the direction of interfragmentary movement (IFM). In this study, combining the characteristics of a new type of external fixator, a genetic algorithm-based method for adjusting the IFM direction for fracture healing is proposed. In this method, the Mechano‐regulatory theory is used to simulate the fracture healing process, with the goal of improving the axial stiffness of the callus, and the optimal IFM direction is then found by utilizing genetic algorithm. The results show that the IFM orientation obtained by the proposed method can increase the axial stiffness of the callus faster. Moreover, it means that the weight-bearing capacity of the tibia can be quickly restored, and the external fixator can be removed as soon as possible, which provides a reference for solving the delayed and non-union problems of oblique fractures.