Poor surface quality in bone surgery affects bone tissue healing and delays recovery time. Combining ultrasonic vibration with conventional drilling helps to improve the surface quality of the boreholes during bone surgery. The ultrasonic vibration assisted drilling test of fresh cortical bone was carried out, and the surface quality was analyzed compared with ordinary drilling; the optimal response surface methodology was used to study the influence of parameters such as amplitude, frequency, spindle speed and feed rate on surface roughness. The results show that better surface quality can be obtained under the condition of ultrasonic vibration loading; and reasonable selection of vibration parameters and cutting parameters can effectively improve the surface roughness of the boreholes.