This article proposes an artillery structural dynamic response optimization method based on the Stackelberg game theory. The artillery multi-flexible body dynamic model is constructed firstly, and the live firing experiment is carried out to verify the accuracy of the constructed model. The multi-objective optimization model of artillery structural dynamic responses is established, and the sensitivity analysis and fuzzy c-means cluster algorithm are used to split the design variable set and, more importantly, transform the optimization model into a two-leader-one-follower Stackelberg game model. The process of solving Stackelberg equilibrium is a bi-level optimization, where the two leaders play a Nash sub-game first and impose the decision to the follower and then the follower makes its own optimization with considering this decision. Until the leaders cannot obtain more profits, the Stackelberg equilibrium is reached. The results demonstrate that the artillery structural dynamic responses have been greatly improved.