This paper presents a practical approach for the multiple response optimizations of operational parameters in the ultrasonic assisted drilling of deep holes. Applying the Taguchi design of experiments, a plan of 27 drilling tests on 6061 aluminium alloy with the depth-to-diameter ratio of 10 was conducted. The responses of cutting force and torque, maximum force and torque, including the chip-evacuation parts which appeared when drilling deep holes, were chosen to be optimized. Three significant drilling parameters, named vibration amplitude, feeding rate and cutting speed were found to have the most significant effects on the output responses. Based on the grey relational grade analysis and analysis of variance technique, optimum levels as well as the percentage contribution of such parameters were identified. Confirmation test was conducted to validate the test result. Experimental results showed that the multi-response optimization problem in ultrasonic assisted the deep hole drilling can be effectively addressed through the combination of Taguchi design and Grey relational analysis.