Aiming at the control problem of CNC machine tool spindle, an comprehensive robust controller was used to achieve effective control of the CNC machine tool spindle, and the control effect was simulated and verified. The schematic diagram of the CNC machine tool spindle system was constructed, and the complete dynamic model of the CNC machine tool spindle considering the cutting force was established. A comprehensive robust controller for the machine tool spindle was developed based on H∞ control strategy. MATLAB was used to simulate the spindle of the CNC machine tool, and the simulation results were compared and analyzed with the traditional PID controller. The results show that the spindle speed of the CNC machine tool controlled by the comprehensive robust controller has a small amount of overshoot, and the fluctuation can be quickly eliminated; the required control voltage range is reduced by about 50%. Even if subjected to large random interference, the spindle system can quickly eliminate interference into a controlled and stable state. The dynamic stability and anti-interference ability of machine tool spindle can be improved by adopting the comprehensive robust controller.