In this paper, a cost analysis of two-stage worm-gear box is presented. The optimal partial transmission ratios are determined to achieve minimum gearbox cost. Nine main parameters, including the total gearbox ratio, the coefficient of helical wheel face width, the allowable contact stress of helical gear set, the output torque, the gearbox housing cost per kilogram, the gear cost per kilogram, the coefficient of worm cost, and the shaft cost per kilogram, are considered in the optimization problem. The screen experiment technique is applied to carry out the design of experiment simulation. Finally, the regression model of the 2nd partial transmission ratio is obtained and utilized to find optimal values for minimizing the gearbox cost. Additionally, the results show that the output torque has the most significant effect on the ratio. The interactions among input parameters are also performed. Moreover, the proposed regression model is validated by the experimental data with excellent agreement.