Abstract: ⁹⁰Y is an ideal therapeutic radionuclide, and its labeled radiopharmaceuticals are widely used in the diagnosis and treatment of a variety of cancers. In order to verify the feasibility of irradiating the 49-2 reactor to produce ⁹⁰Y isotopes, the activity of irradiating high-purity yttrium oxide (Y₂O₃) targets to produce radioisotopes ⁹⁰Y in the 49-2 core was calculated by using the Monka program MCNP6 (Monte Carlo N-particle 6) and SCALE6.1. It was compared with the results of irradiation experiments at the H8 position. The theoretical calculation results show that E8 and H8 pores can produce ⁹⁰Y (>10 Ci/gY) with high specific activity, the irradiation time required is 2 days and 6 days, respectively, and the content of impurity nuclides in the radioactive isotope ⁹⁰Y produced by irradiation is low (<10⁵). Compared with the results of ⁹⁰Y irradiation experiment at H8 hole in the reactor of 49-2, the deviation was 4.02%. The results show that ⁹⁰Y isotopes that meet medical requirements can be produced by irradiating high-purity yttrium oxide targets with 49-2 reactors.