Abstract: For lunar exploration projects, this paper proposes a series of novel leak detection methods targeted for the plutonium 238 radio-isotope thermo-electric generator(RTG) load embedded with argon working fluid, the biological science payload embedded with air working fluid, and the characteristics of the thermal control fluid circuit based on the perfluorotriethylamine working fluid. The above-mentioned technologies for the argon gas refrigerant leak detection, the air refrigerant leak detection, and the liquid perfluorotriethylamine refrigerant leak detection have been successfully applied in the lunar exploration missions.