Objective:To evaluate the efficacy of apatinib combined with 131I therapy for progressive metastatic differentiated thyroid cancer (pmDTC). Methods:Seven patients (1 male, 6 females, age: 58(51, 66) years) with pmDTC in Nanjing First Hospital between November 2017 and February 2022 were enrolled. Patients received oral apatinib 500 mg once daily. The effect of apatinib on differentiated thyroid cancer were evaluated by using 18F-FDG PET/CT or CT at 3(2, 4) months after the treatment. Then in the state of continuous administration of apatinib, 131I therapy was initiated. 18F-FDG PET/CT or CT was performed at 3 months after apatinib combined with 131I therapy to evaluate the response. Both thyroglobulin (Tg) and Tg antibody levels were monitored every 4 to 8 weeks after the treatment. Wilcoxon signed-rank test was used for data analysis. Results:Five patients achieved partial response after 3(2, 4) months of apatinib treatment and two patients had progressive disease. The disease control rate and objective response rate were both 5/7. Five patients achieved partial response and two patients were in stable disease after apatinib combined with 131I therapy for 2(1, 2) times, with disease control rate and objective response rate of 7/7 and 5/7, respectively. The Tg level declined from 8 644(2 504, 16 300) μg/L (baseline) to 143(7, 3 574) μg/L( z=-2.37, P=0.018) after apatinib combined with 131I therapy. In addition, one patient had a significant increase in 131I uptake in the tumor lesions after long-term treatment with apatinib. Conclusions:Apatinib has obvious anti-tumor effects and high objective response rate is observed after apatinib treatment in patients with pmDTC. The anti-tumor effects are more prominent after combined with 131I therapy. Long-term treatment with apatinib may alter the tumor microenvironment to induce differentiation and increase iodine uptake in tumor lesions, which need to be further studied.