Abstract: The structural design of airborne equipment should meet the fatigue life requirement under the durable random vibration. The first-time success rate of projects can be improved effectively by predicting the weak area of the structure accurately and optimizing it through simulation. On the basis of the frequency domain fatigue analysis method, combined with Miner’s linear cumulative damage theory and the S-N curve of materials, the fatigue life of a mounting frame under random vibration is analyzed in this paper. The fatigue life and failure location of the mounting frame obtained by simulation are in good agreement with the test results. The fatigue failure mechanism of the mounting frame is analyzed and the optimization design is carried out. The results show that the vibration fatigue life of the optimized structure is improved significantly.