This study investigates the sensitive region and safe operation voltage of single-event burnout (SEB) in lateral depletion-mode Ga2O3 MOSFET devices via technology computer aided design simulation. Based on the distribution of the electric field, carrier concentration, and electron current density when SEB occurs, the radiation damage mechanism of SEB is proposed. The mechanism of SEB in Ga2O3 MOSFET was revealed to be the result of a unique structure without a PN junction within it, which possesses gate control ability and exerts a significant influence on the conduction of the depletion region. [ABSTRACT FROM AUTHOR]