In the design process of lattice shell structure, the joint is assumed to be ideal rigid, and the bar section design is carried out by considering the three aspects of bar strength, bar stability and overall stiffness. However, for single-layer lattice shell structure, especially for long-span single-layer lattice shell structure, even if the requirements of strength, stiffness and bar stability are met, the overall stability of the structure may not meet the design requirements. However, the current design specification of JGJ7-2010 Technical Specification for Space Grid Structure (Industrial standard of the People’s Republic of China, in JGJ7-2010 Technical specification for space grid structure. China Architecture and Building Press, Beijing 2010 [1]) only limits the stability requirements of single-layer lattice shell structure to the checking of stable bearing capacity, and there is no corresponding anti-instability design method. In the study of the size optimization of lattice structure, the overall stability of the structure is generally expressed as a linear eigenvalue problem, and is processed as an optimization constraint condition rather than an optimization target. In the optimization design method that directly takes the structural stability bearing capacity as the optimization target, the optimization object is often a simple articulated structure, or the calculation time is difficult to meet the requirements of practical engineering design. Based on the instability mechanism of lattice shell structure, the optimization model of single-layer lattice shell structure is proposed by calculating the simple gra_rmin to represent the degree of structural stiffness degradation, and the goal is to reduce the instability trend of the structure. The optimization variable is the bar section. In order to consider the actual construction demand, the bar section is taken from the Chinese manufacturing standard GB/T 17395-2008 Seamless Steel Tube Dimensions, Configuration, Weight and Allowable Deviation (National Standard of the People’s Republic of China, GB/T 17395-2008 Dimension, shape, weight and allowable deviation of seamless steel pipes. Standards Press of China, Beijing 2008 [2]), which is a discrete variable. The constraint conditions are the design constraint conditions and steel quantity constraint conditions stipulated in the specification. In view of the problems of many variables in the stability optimization model of lattice shell structure and the low efficiency of the traditional optimization algorithm, the random mutation operation in the standard genetic algorithm is improved in this chapter, and the guided genetic algorithm for the stability optimization of large single-layer lattice shell structure is proposed. Finally, the stability optimization design is carried out with three single-layer lattice shell structures of different spans as an example.