Objective:To investigate the effects of thyroid-stimulating hormone (TSH) suppressive therapy on the expression of programmed death ligand 1 (PD-L1) and matrix metalloproteinase 2 (MMP-2) in thyroid cancer tissue and prognosis.Methods:A total of 102 patients with thyroid cancer who underwent surgical resection in Weihai Central Hospital, Qingdao University from April 2016 to April 2018 were included in this study. They were divided into a hormone replacement group and a TSH suppressive therapy group ( n = 51/group). The hormone replacement group was given hormone replacement therapy after surgical resection, and the TSH suppressive therapy group was given TSH suppressive therapy. The expression of PD-L1 and MMP-2 in the pericancerous tissue was compared between the two groups during surgery and 3 and 6 months after surgery. Tumor recurrence and metastasis were compared between the two groups after 6 months, 1 year, and 3 years of follow-up. Results:At 3 and 6 months after surgery, the PD-L1 positive expression rate in the TSH suppressive therapy group was 9.8% (5/51) and 13.7% (7/51), respectively, and the MMP-2 positive expression rate in the TSH suppressive therapy group was 9.8% (5/51) and 13.7% (7/51), respectively, which were significantly lower than 25.5% (13/51), 31.4% (16/51), 27.5% (14/51), and 33.3% (17/51) in the hormone replacement group ( χ2 = 4.32, 5.24, 4.55, 5.45, P = 0.038, 0.022, 0.033, 0.020). At 3 years after surgery, the tumor recurrence and metastasis rate in the TSH suppressive therapy group was 5.9% (3/51), which was significantly lower than 17.6% (10/51) in the hormone replacement group ( χ2 = 4.32, P = 0.038). Conclusion:For patients with thyroid cancer undergoing surgery, TSH suppressive therapy can better inhibit the expression of PD-L1 and MMP-2 in thyroid cancer tissue, reduce the risk of long-term recurrence and metastasis, and have a better clinical application value for improving the prognosis compared with hormone replacement therapy.