Abstract: In neurosurgery, skull repair caused by surgical approach is one of the important research contents. In this paper, a rapid reconstruction method of the skull defect with optical navigation system is proposed. This method can automatically reconstruct the structure of skull defect with the intraoperative defect edge points and preoperative medical image data. The head model experiment was used to evaluate the effect of the method, the average error of the reconstruction of the defect in the right orbit was 0.424 mm, while the average error of the reconstruction of the defect in the posterior skull base was 0.377 mm. The experimental results show that the structure of the defect is consistent with the actual defect, and the reconstruction accuracy satisfies the clinical requirements in neurosurgery.