. In this study, the prediction models of thrust force, tool wear and torque in drilling nickel-based alloy GH536 are developed based genetic algorithm and drilling experiments. Tool wear value is used as constraint condition and maximum cutting efficiency as goal to optimize drilling process parameters. In addition, the relationship between tool life and cutting efficiency is analyzed by exploiting the tool wear prediction model. The results of the analysis show that under the condition of efficiency remains unchanged, the tool life can be increased by increasing drilling speed and appropriately reducing feed rate, these results are consistent with the optimized process parameters.