GaN HEMT devices are sensitive to the single event effect (SEE) caused by heavy ions, and their reliability affects the safe use of space equipment. In this work, a Ge ion (LET = 37 MeV·cm2/mg) and Bi ion (LET = 98 MeV·cm2/mg) were used to irradiate Cascode GaN power devices by heavy ion accelerator experimental device. The differences of SEE under three conditions: pre-applied electrical stress, different LET values, and gate voltages are studied, and the related damage mechanism is discussed. The experimental results show that the pre-application of electrical stress before radiation leads to an electron de-trapping effect, generating defects within the GaN device. These defects will assist in charge collection so that the drain leakage current of the device will be enhanced. The higher the LET value, the more electron–hole pairs are ionized. Therefore, the charge collected by the drain increases, and the burn-out voltage advances. In the off state, the more negative the gate voltage, the higher the drain voltage of the GaN HEMT device, and the more serious the back-channel effect. This study provides an important theoretical basis for the reliability of GaN power devices in radiation environments.