The high-cycle fatigue properties and crack initiation and propagation behavior of 2397-T87 Al-Li alloy were investigated. The results show that when the stress ratio R is 0.1, the fatigue limit of smooth specimens of 2397-T87 Al-Li alloy in the L orientation, LT orientation and ST orientation are about 192 MPa, 243 MPa and 151 MPa respectively. The fatigue limit of notch specimens in the L orientation, LT orientation and ST orientation are about 72 MPa, 78 MPa and 70 MPa respectively. Fatigue crack initiation of this alloy mainly occurred on the sample surface, with initiation from the defects caused by the oxides and inclusions, the Al(CuMnFe) secondary phases. Persistent slip bands (PSB) and grain orientation have important influence on fatigue crack propagation at early stage.