Objective To study the effect of curcumin on the radiosensitivity of the human papillary thyroid cancer cell line TPC?1, to investigate the signaling pathway probably targeted by curcumin, and to provide new insights for the development of radiosensitizers for thyroid cancer. Methods The human papillary thyroid cancer cell line TPC?1 was treated with curcumin and radioactive iodine. CCK?8 assay, colony formation assay, and flow cytometry were used to evaluate cell proliferation, colony formation ability, and cell apoptosis, respectively. Western blot was used to measure the expression of p50, p65, and apoptosis?related proteins, Bcl?2 and Bax. Cell proliferation, colony formation ability, and cell apoptosis were determined again after the activity of the NF?κB signaling pathway was blocked by a NF?κB signaling pathway inhibitor PDTC. Results After treatment with curcumin and radioactive iodine, the human papillary thyroid cancer TPC?1 cells had reduced cell proliferation and colony formation, an elevated apoptosis rate, downregulated expression of anti?apoptotic Bcl?2, and upregulated expression of pro?apoptotic Bax in a dose?dependent manner. These results indicated that curcumin enhanced the radiosensitivity of TPC?1 cells. Curcumin inhibited the activation of the NF?κB signaling pathway in the TPC?1 cells treated with radioactive iodine. When the activity of the NF?κB pathway was blocked by PDTC, cell proliferation and colony formation were reduced and the apoptosis rate was increased, indicating an enhanced radiosensitivity of TPC?1 cells. Conclusions Curcumin is likely to target the NF?κB signaling pathway. It regulates the radiosensitivity of thyroid cancer cells by inhibiting the activity of the NF?κB signaling pathway.