The structures of civil aircraft must maintain high safety level and high reliability during the expected service life. The objective of fatigue design for aircraft structure is to ensure the good fatigue property of the structures. Fatigue strength design is a method of enhancing the fatigue property of the structures. In this paper, a structural optimization for web lap splice of pressure bulkhead of a certain type airplane was proposed and FEM was used to calculate the load distribution among the lap splice fasteners of original structure and optimized structure. Then the fatigue analysis was performed. After that the crack growth analysis were performed by using NASGRO for both configurations. The analysis results show that the optimization design can improve the fatigue and damage tolerance properties significantly and reduce the weight and maintenance cost of the structure as well.