The missile safety and reliability play important roles in its evaluation and design. Failure or inaccuracy of initiation is an occasional but extremely troublesome hazard in weapon system safety. The uneven fuel distribution and uncontrollable motion of initiation structure are both the causations of this hazard in a double-event fuel-air explosive missile application. Thus, it is crucial to implement the coupling between the initiation structure and the fuel field to succeed in a reliable application. This paper employs CFD to simulate the explosive dispersal process of fuel and uses MATLAB to investigate the motion trajectory of the initiation structure. As for the solid-liquid fuel com-posed of 50 % aluminum powder and 50 % propylene oxide, its optimal concentration for reliable initiation is 186 275 g/m 3 . In the case of a 200 kg missile with a speed of 300 m/s, the results imply that, at 250 ~300 ms which is a reliable initiation time, the initiation structure gets to the reliable range of 10.8 ~14.1 m where the fuel concentration approaches to the optimal range for initiation. Ultimately, for any missile development, the coupled simulation-based approach is summarized to prevent the initiation failure and enhance its inherent safety, so as to avoid accident casualties and property loss.