Isotope production includes reactor irradiation production (“pile light“ isotope), accelerator bombarding target production (“instrument light” isotope), and spent fuel extraction. Among them, the radioisotope produced by reactor irradiation is one of the most important ways of radioisotope production at present, with large output, large variety and low scale production cost. The production of isotopes by reactor irradiation is based on neutron capture in the target material by bombarding it with thermal neutrons to excite or produce radioactive isotopes from the fission of the target material. However, the radiation target of the isotope is neutron absorber, and the physical thermal state of the reactor will change during loading, fixing and moving out of the irradiation channel, which may affect the operation safety of the reactor. Therefore, the analysis and demonstration of physical thermal safety in the process of isotope production is an essential and important link. In this paper, the physical thermal safety analysis of different radioisotope production at home and abroad is investigated, and the safety problems, safety criteria and demonstration methods of radioisotope production are summarized. At the same time, the preliminary physical thermal safety analysis scheme of radioisotope production by HTR-PM is proposed in combination with the physical thermal safety characteristics of HTR-PM reactor. This review provides reference for the future physical thermal safety analysis of radioisotope production.