It is easy to cause thermal damage to the bone tissue when the surgical robot performs skull drilling to remove bone flaps, due to the large diameter of the drill bit, the large heat-generating area, and the long drilling time. Therefore, in order to reduce the thermal damage during the robot-assisted skull drilling process, the relationship between the drilling parameters and the drilling temperature during the skull drilling was studied in this paper. Firstly, a dynamic numerical simulation model of the skull drilling process was established by ABAQUS, and a temperature simulation plan for skull drilling was designed based on the Box–Behnken method. Then according to the simulation results, a quadratic regression model of drill diameter, feed rate, drill speed, and drilling temperature was established by using the multiple regression method. By analyzing the regression model, the influence of drilling parameters on the drilling temperature was clarified. Finally, the bone drilling experiment was carried out, and the error percentage was lower than 10.5% through the experiment to verify the reliability of the conclusion, and a safety strategy was proposed to ensure the safety of the surgical drilling process based on this experiment.