Objective To explore the improvement of thyroid function of gas signal molecule hydrogen sulfide (H2S) in Graves hyperthyroidism (GD) mice and its protective effect on thyroid follicular cell damage. Methods 45 BALB/c mice were randomly divided into normal control group, empty vector virus group and recombinant adenovirus group. GD mouse model was established by injection of AdTSHR289 recombinant adenovirus. The mice successfully modeled by GD were randomly divided into model group, H2S group and methabazole group. The mice in the imidazole group were given intraperitoneal injection of mesozole solution (39mg/kg/d), and the mice in the normal control group and the empty vector virus group were given intraperitoneal injection of an equal volume of 0.9% Nacl solution for 4 weeks. After 4 weeks, serum thyrotropin receptor antibody (TRAb), thyroxine (T4) and thyroid stimulating hormone (TSH) levels were measured. HE staining was used to observe the pathological changes of thyroid tissue in each group of mice. Immunohistochemical staining was used to detect the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 (CyclinD1) in thyroid tissue. Western blot was used to detect the expression levels of sodium/iodine transporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (Tg). Isolate and culture mouse thyroid follicular epithelial cells, and randomly divide the cells into normal control group, H2O2 group and NaHS+H2O2 group. The cells in the normal control group did not undergo any treatment. The H2O2 group used H2O2 solution to treat the thyroid follicular epithelial cells for 24 hours. The NaHS+H2O2 group first treated the thyroid follicular epithelial cells with NaHS for 30 minutes and then treated the cells with H2O2 solution. The cell activity of each group was detected by CCK8 method, flow cytometry was used to detect the apoptosis of each group. Results Compared with the normal control group, the levels of TRAb and T4 in the serum of mice in the recombinant adenovirus group increased significantly (P＜0.05), TSH level decreased significantly (P＜0.05). After the intervention of NaHS solution, the levels of TRAb and T4 in the serum of GD mice decreased significantly (P＜0.05), TSH level increased significantly (P＜0.05), the thyroid tissue lesions were significantly improved, and the positive expressions of PCNA and CyclinD1 were significantly reduced (P＜0.05), the expression of NIS, TPO and Tg protein decreased significantly (P＜0.05). Compared with the normal control group, the activity of thyroid follicular epithelial cells in the H2O2 group decreased significantly at 24, 48 and 72 hours of culture (P＜0.05), the apoptosis rate increased significantly (P＜0.05); Compared with the H2O2 group, when the cells in the NaHS+H2O2 group were cultured for 48h and 72h, the activity of thyroid follicular epithelial cells increased significantly (P＜0.05), and the apoptosis rate decreased significantly (P＜0.05). Conclusion The gas signal molecule H2S has a certain improvement effect on hypothyroidism in GD mice. The mechanism may be related to the inhibition of PCNA, CyclinD1 and NIS, TPO, Tg protein expression, and it has a protective effect on H2O2induced thyroid follicular epithelial cell damage.