The hydrogen-powered high-speed train (HPHST) is a kind of environmentally friendly and efficient transportation equipment, but too complicated components and interaction relationships between them may affect its reliability. Thus, this paper studies the reliability optimization of the HPHST through the optimal structure design. First, an interdependent machine-electricity-communication-gas network (IMECGN) is constructed based on the four types of the components and the interaction relationships between them to model the HPHST and its reliability is measured by the weighted network efficiency considering the interdependency and practical meaning of the components. Then, a simulated annealing algorithm for optimizing the network structure is presented by swapping edges. Finally, a real-world case study is performed to demonstrate that the proposed structure optimization approach can greatly enhance the reliability of the HPHST. In addition, for the optimized IMECGN, the component having the high weight intends to reconnect to a similar one. This work should be helpful for guiding the optimal structure design for the highly reliable HPHST.