As the blade surfaces of the centrifugal impeller are normally twisted in design to achieve the required performance, it can cause overcut and collision problems during machining. In order to comprehend the design concepts of impeller and create the capacity of the manufacture, the objectives of this paper are the regeneration of impeller profile and the studies of the five-axis NC machining. The geometry of the impeller is modeled according to the reverse engineering firstly. In the machining process, the flank cutting technique and the point cutting method are applied to rough and finish machining processes. Through the application of CAM software, the interference-free toolpath and the cutter location for five-axis NC machining are generated. To avoid collision between machine tool components, the generated toolpath is verified before actual machining through solid cutting simulation. It is also verified through the real cut with model material on a five-axis machine tool.