Because of the complexity of five-axis ball-end milling process, it is difficult to control the quality of the finished parts. It is well known that one of the most important differences between 5-axis and 3-axis CNC machining is whether tool-axis vector is variable in milling process. In this paper, the tool orientation is researched in order to obtain desired surface quality and improve production efficiency. And the influence of tool inclination angle on surface integrity, especially surface topography/roughness and residual stress in high-speed milling of P20 die steel is studied by means of milling experiments including 8 cases of ball-end milling of freeform surface. Finally, the optimal tool inclination angles including lead angle and tilt angle and milling method were obtained for 5-axis ball-end milling. And in the meanwhile, cutting condition can be improved and better surface quality can be obtained by selecting reasonable tool inclination angles and up/down milling method.