Abstract: To complete the production of radioisotope ⁶³Ni based on self-reliance, the reactor physical calculation program is used to establish a balanced core model of HFETR. The process of irradiating natural nickel and high-purity ⁶²Ni to produce ⁶³Ni at four typical in-pile locations is simulated. The results show that high purity ⁶²Ni is the most suitable target material. The central channel of K14 fuel element is the best irradiation position. The high specific activity ⁶³Ni (≥5.55×10¹¹ Bq/g) is produced by high purity ⁶²Ni target with irradiation time about 60 cycles; The radioactive isotope ⁶³Ni produced by irradiation has low impurity nuclide content; The target at K14 position during the irradiation has the highest heat release rate of 9.73 W/g. Furthermore, a continuous batch production plan for segmented loading and segmentation is proposed, which can provide technical support for the subsequent engineering production line design.