Background: The majority of differentiated thyroid cancer (DTC) has good prognosis after a careful standardized therapy according to the current guidelines. However, approximately 13% to 15% of DTC shows surprisingly aggressive behavior and invades the surrounding structures, and then a few is very difficult to remove. In that specific context, preoperative neoadjuvant targeted therapy may improve the clinical stage and create an opportunity for operation.Case presentation: We reported a case of 64-year-old woman with locally advanced papillary thyroid cancer (PTC) who presented with dysphagia due to seemingly unresectable tumor, which severely invaded the left esophagus at the junction of neck and thorax, difficult to undergo a safe and complete removal. With an approvement of institution ethics committee, this patient was treated with neoadjuvant therapy (apatinib 500mg orally qd).Six weeks later, the tumor dramatically shrunk from 56*37mm to 29*26mm with well-controlled mild hypertension. After 10 days interval of apatinib withdrawal, complete tumor excision was accomplished without esophagus fistula. Postoperative inhibition and radioiodine 131I ablation were performed. At one-year follow-up evaluation, no tumor recurrence or metastasis was observed.Conclusion: Preoperative short-termed targeted treatment for locally advanced inoperable DTC may become a promising neoadjuvant therapy, which can reduce the tumor size and decrease stage, thus being convenient for complete and safe removal.