Aiming at the optimization design of spindle, this paper introduces deflection constraint, strength constraint, corner constraint, cutting force constraint, the limit of torsional deflection, boundary constraint of design variable, dynamic property constraint , realizes the expression of the mathematical model of the spindle optimization design. Through the introduction of the real number code rule, the selection operator is built by adopting the optimum maintaining tactics and proportional selection, the crossover operator is built by using the method of arithmetic crossover and the mutation operator is built by using the method of uniform mutation. In the platform of VC++, the system of spindle optimization design based on GA is built. The analysis of the example shows that using the genetic algorithm to optimize the spindle can ensure the convergence of the optimization course, expand the search space, and the effect of optimization is obvious.