Objective To analyze the abnormality of radiation damage sensitive indices in radiation workers after operation of a third-generation nuclear power plant in Guangdong Province, China, and to provide a basis for promoting the occupational health management of radiation workers. Methods A two-way cohort study (2019—2021) was conducted to compare the radiation sensitive indices of occupational health examination in the exposed group (453 subjects) and the control group (160 subjects). Results In 2021, the free triiodothyronine (FT3) level of the exposed group was significantly higher than that of the control group [(5.57 ± 0.56) pmol/L vs (5.42 ± 0.60) pmol/L, t = 0.59, P < 0.05]. From 2019 to 2021, the exposed group showed significant changes in the average levels of platelet, hemoglobin, FT3, free thyroxine (FT4), and thyroid-stimulating hormone (P < 0.05); FT3 and FT4 first increased and then decreased, while TSH decreased continuously. Conclusion Long-term exposure to low-dose ionizing radiation from nuclear power plants can affect the platelet, hemoglobin, FT3, FT4, and thyroid-stimulating hormone of radiation workers, and the effect is relatively prominent on thyroid function by causing a tendency to hypothyroidism.