The Monte Carlo simulation (MCS) can provide high reliability evaluation accuracy. However, the efficiency of the crude MCS is quite low, in large part because it is computationally expensive to evaluate a very small failure probability. In this paper, a subset simulation-based reliability analysis (SSRA) approach is combined with multidisciplinary design optimization (MDO) to improve the computational efficiency in reliability-based MDO (RBMDO) problems. Furthermore, the sequential optimization and reliability assessment (SORA) approach is utilized to decouple an RBMDO problem into a sequential of deterministic MDO and reliability evaluation problems. The formula of MDO with SSRA within the framework of SORA is proposed to solve a design optimization problem of a hydraulic transmission mechanism.