ObjectiveTo evaluate the safety and efficacy of lenvatinib as targeted therapy for locally advanced thyroid cancer. MethodsThe data of 17 patients with locally advanced thyroid cancer who received targeted therapy in the Department of Head and Neck Surgery, Clinical Oncology School of Fujian Cancer Hospital from September 2021 to June 2023 were prospectively collected and analyzed. ResultsSeventeen patients received lenvatinib for a median of 8 weeks (4–32 weeks), 5 patients achieved partial response, 11 patients achieved stable disease, and 1 patient experienced progressive disease. The objective response and disease control rates were 29.4% (5/17) and 94.1% (16/17) respectively, the median tumor diameter of the target lesion decreased from 43 mm before treatment to 12 mm after treatment. Five patients did not undergo surgery because of tumor progression and their refusal; R0/1 resection was achieved in 11 of the 12 remaining patients (91.7%). All patients suffered from drug-related adverse events, and the commonest drug-related adverse events were hypertension (7/17, 41.2%), diarrhea (6/17, 35.3%), and proteinuria (5/17, 29.4%). There were no major drug-related adverse events. ConclusionPreliminary analysis indicates that lenvatinib is effective and safe for targeted therapy of locally advanced thyroid cancer, with a relatively high rate of R0/1 resection.