As one of the key components of the nuclear power equipments, the nuclear channel head has a complicated shape and is difficult to be machined. In this paper, the optimal combination of cutting parameters of large-scale nuclear channel head is researched. Considering the machining requirements and machining conditions, the cutting parameters optimized mathematical model is established to achieve the goal of maximum production efficiency. Meanwhile, the target functions and the corresponding constraint functions are analyzed. Finally, by using genetic algorithm of simulating biological evolution, the mathematic models of cutting parameters of CNC machining are compared and optimized. Then the optimized results are compared with the cutting parameters obtained through the trial-producing experience and manual of a small-size channel head. We conclude that the optimized cutting parameters can greatly increase the CNC machining efficiency of Nuclear Channel Head.