Abstract: ⁶³Ni is an important industrial radioisotope, which has the characteristics of long half-life, moderate power density and easy to manufacture. ⁶³Ni is a promising β radiation source with low energy. The characteristics of irradiation production of ⁶³Ni with high specific activity in high flux reactor are studied, and the influence of neutron flux, neutron energy spectrum, irradiation target design scheme on the specific radioactivity are analyzed. On this basis, the ideas of irradiation scheme design for further improving the specific activity of ⁶³Ni are discussed. The research shows that ultra-high flux reactor helps to improve the specific activity of ⁶³Ni. The results provide references for the irradiation production scheme design of ⁶³Ni.