Abstract: The large-scale production of ²⁵²Cf mainly depends on irradiating targets in high flux reactor. The production of ²⁵²Cf has the characteristics of complex conversion chain, more intermediate nuclides and remarkable fission losses of target feedstock, which brings great challenges to further improve the production of ²⁵²Cf. The factors affecting ²⁵²Cf production were analyzed, including neutron flux level, neutron energy spectrum distribution, target type and structure, etc. The study shows that neutron flux and energy spectrum distribution have a significant impact on ²⁵²Cf’s amounts, and the output could be further improved by utilizing target with heavy nuclei or the target in annular shape. The results could provide references for irradiation scheme design of producing ²⁵²Cf in high flux reactors.