The vibration signal of the main shaft gearbox is greatly affected by external factors, which leads to a low fault diagnosis accuracy rate. This paper proposes to diagnose the fault of the spindle box based on the speed signal collected by the virtual prototype. Firstly, the virtual prototype of main gearbox is built, and the contact parameters of gear pairs were set based on Hertz contact theory, and the accuracy of the model simulation is verified by comparing the theoretical speed. Secondly, by simulating the common fault types of a variety of gearboxes, the trend of the output speed of each shaft under different working conditions is analyzed. Finally, a KNN fault diagnosis model is established based on simulation samples, and the Z-Score method is improved. The results show that the diagnosis accuracy of the improved fault model is significantly improved, which realizes the correct diagnosis of common faults of the gearbox.