In order to investigate the effect of hole expansion strengthening of split mandrel with different relative expansion amount on the fatigue properties of 7050 aluminum alloy, a finite element model of hole expansion strengthening of split mandrel was established, and hole expansion strengthening of split mandrel experimental was carried out. The residual stress on the hole wall of the hole expansion strengthening specimen and the distribution law of the stress on the hole wall of the loaded specimen were analyzed. In addition, the relationship among relative expansion amount, residual stress and fatigue life was explored. Finally, the resist fatigue effect of hole expansion strengthening of split mandrel was revealed. The results showed that, the relative expansion amount of 2%, 3%, and 4%, while the maximum residual compressive stress of the hole wall were 246.8, 338.6, and 367.7 MPa at the inlet area of the hole wall of the specimen. The relative expansion amount was positively correlated with the maximum residual compressive stress of the hole wall. Inlet area of the hole wall of the loaded specimen, the relative expansion amount of 2%, 3%, and 4%, and the maximum stress of the hole wall were 451.2, 368.7, and 321.6 MPa, the relative expansion amount was negatively correlated with the maximum stress of the hole wall. The median fatigue life of specimen with relative expansion amount of 2%, 3%, and 4% is 1.17, 1.52, and 1.71 times of that of with relative expansion amount of 0.