A reliability-based multidisciplinary design optimization (RBMDO) frame work for Centrifugal compressor was presented. Multidisciplinary feasible method was used to decouple the multidisciplinary analysis and the fourth moment method for reliability analysis was recommended systematically. Based on the approximation, the RBMDO framework was finished. The case study shows that optimization efforts could improve obviously the performance of centrifugal compressor under the requirements of reliability. This framework could make the design reach the best performance with a good reliability. It indicates that the proposed optimization method is available and feasible for the engineering application.