Abstract: In the field of multi-axis milling, tool inclination is one of the key factors affecting the mechanical response and workpiece surface quality. The specific influence of the change of the lead angle and the tilt angle on the cutting speed of the in-cut cutting edge was analyzed based on theoretical modeling. The effect laws of the inclination angle of the dynamic response of the milling force and the surface morphology and roughness of the workpiece were researched based on the cutting experiment under the angle of ± 15°, ± 30°, ± 45°and ± 60°. The results show that, compared with the lead angle α, the change of tilt angle β is more significant on the vibration effect in the cutting process. When the tilt angle β is between −30° and 45°, and the lead angle α is between −60° and 45°, it is better to suppress the negative effect of milling force fluctuations on the machining process. When the inclination angle is −30° and 30°, the maximum axial milling force is significantly reduced, which is beneficial to prolong the tool life. When the lead angle α is between 30° and 60°, it can effectively reduce the number of squamous defects and improve the surface quality of the workpiece.