Aiming at the CNC machine tool’s machining accuracy demand problem caused by manufacturing intelligentization, an intelligent design optimization system for CNC machine tool’s feed mechanism was constructed. The intelligent design optimization system consisted of requirement analysis module, conventional design module, intelligent optimization module and design resource center, so it can realize knowledge integration, data exchange and model sharing during the design process of CNC machine tool feed mechanism. To meet the dynamic and static performances requirement of CNC machine tool’s feed mechanism, parametric modeling, finite element simulation and thermal-mechanical coupling analysis were conducted, which provided theoretical basis for the optimization design of feed mechanism. On the basis of conducting conventional design for CNC machine tool feed mechanism, sensitivity analysis method, back-propagation neural network and genetic algorithm were used to carry out structural multi-objective optimization for feed mechanism, which improved the intelligent design level of system. Using the constructed system to conduct intelligent design optimization for the Y-axis feed mechanism of a precision gantry CNC machine tool, the dynamic and static performances of the feed mechanism were improved. After conducting experiment on the feed mechanism, the comparison of the optimization result with the experimental value indicated that the intelligent design optimization system was reasonable and feasible.