Abstract: This article takes the key mechanical problems in the structural design of the core module of the China’s space station (CSS) as an example, and introduces the important applications of mechanical theoretical models, calculation methods and experimental techniques in the structural design of spacecraft. It elaborates on the configuration of the three-module and three-ship structure of the CSS, the structural form of the Tianhe core module, the specific measures to reduce structural weight and improve the load-bearing ratio, the full-scale fatigue experimental method of the core module on the ground simulating the space environment, and the development trend of innovating strength design to fatigue damage tolerance design based on fracture mechanics. It summarizes the key role of mechanics in the design of the CSS.