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In order to improve the machining accuracy of CNC machine tool and promote manufacturing industry upgrade development, a CNC machine tool spindle optimization design expert system was studied. On the basis of the rich CNC machine tool spindle design experience in current, mechanical dynamics, optimization method and fuzzy logic theory, a spindle transmission type fuzzy optimum seeking method was developed. Taking the dynamic and static performance of CNC machine tool spindle as optimization goals, and adopting the sensitivity analysis to choose the design variables, a mathematic model of the spindle structural multi-objective optimization design was established. A gradual optimization algorithm was put forward to solve the optimization model, and a new kind of spindle structural optimization design method was obtained. Through integrating the “spindle transmission type fuzzy optimum seeking method” with the “spindle structural optimization design method”, the CNC machine tool spindle optimization design expert system was developed. Taking the multi-objective optimization design for a precision CNC machine tool spindle as application case, the optimization design results were compared with the actual situation and the experimental results, which verified the feasibility of the CNC machine tool spindle optimization design expert system.