Reliability of design result is impacted by uncertainty of design variables in multidisciplinary design optimization (MDO) of cruise missile, which can't be solved using traditional MDO. The reliability optimization method based on sequential optimiza tion and reliability analyses (SORA) integrates optimization design and reliability analyses. Considering uncertainty of design varia-bles in optimization, and design result was searched by single cycle form. From the example of MDO of cruise missiles, it is known that the SORA based reliability optimization method can not only reduce the effect of uncertainty of design variable on design re sult, but also improve the reliability.