Abstract: In order to explore effect of laser cutting on fatigue performance of aircraft fuselage skin, by using the method of simulation and contrast test method respectively, fatigue performance of aircraft skin material was studied by theoretical analysis and experimental verification. Analysis data of finite element fatigue of aircraft skin material, and comparison data of fatigue performance test of laser cutting specimen and mechanical milling specimen were obtained. At the same time, fatigue fracture of aircraft skin plate was scanned and analyzed by scanning electron microscope. The analysis results show that after laser cutting, fatigue life of aircraft skin material is about 5.4104. After mechanical milling, fatigue life is 2.34105. Laser cutting has a certain impact on fatigue performance of aircraft fuselage skin materials, but its fatigue life can increase through grinding and processing of cutting seams.