The vibration of machine tool spindle is very important for machining. Firstly, in order to explore the relationship between spindle vibration and process parameters, the spindle vibration acceleration when polishing aero-engine blade was measured, and the quadratic polynomial models between the spindle vibration acceleration in X, Y and Z direction and the process parameters were established. Secondly, a quadratic polynomial model for the influence of process parameters on polished surface roughness was also determined. Thirdly, through the Analysis of Variance (ANOVA) and main effect analysis, it can be seen that the spindle speed has the greatest impact on the vibration. Finally, a multi-objective optimization model was established with the optimization objective of minimizing spindle vibration acceleration and polished surface roughness, and the optimal process parameters were solved using genetic algorithm. The optimal process parameters were verified and the results show that the polished surface roughness with the optimal process parameters are all less than 0.4 μm, and the deviation rates between the theoretical optimization results of spindle vibration acceleration and the experimental results are all less than 10%, indicating that the optimization results are good.