A radiation hardening pre-regulated high voltage power supply is studied. The factors affecting the output voltage before and after neutron irradiation are analyzed. The radiation effect of key component transistor is analyzed and verified by experiments. Two optimization measures for static work point optimization and Darlinton transistor structure are put forward. The validation prototype is fabricated, and the experimental results after 1 MeV equivalent neutron 2×1013n/cm2 flux coincide with the theoretical analysis values, which confirms the effectiveness of radiation hardening measures.