Based on the working principle and working process of the tire building machine, the spindle model of the tire building machine was established by analyzing the load of the spindle. Utilizing COSMOS to do the FEM analysis, the structural optimization was carried out. The deflection of the spindle determining the precision of the tire should be minimized. Meanwhile, in order to reduce the cost of the spindle, the volume of the spindle should be minimized. In this paper, the weighted coefficient method was applied to solving this multi-objective optimization problem. As no ready-made formula was found for the deflection of the spindle, the following method was adopted. Firstly, the calculation in COSMOS with different values was conducted, and then the curve fitting was finished in MATLAB to get the formula between defection and diameter of bore, and finally the optimization of the volume and defection was achieved.