Objective: The study aims to evaluate the accuracy of the cytological diagnosis using SurePath-liquid based cytology (SurePath-LBC) in fine needle aspiration (FNA) for thyroid nodules. Method: 352 patients who underwent thyroidectomy were recruited at the First Affiliated Hospital of Nanjing Medical University with complete data of cytopathology and histopathology. We compared the cytological diagnosis using SurePath-LBC preoperatively to the final surgical pathology. 363 independent cytology reports were obtained from these patients. 264 cases were detected for BRAFV600E mutation status. Result: 112 cytopathology reports were reported as “suspicious for malignancy, SM” with 110 cases suspicious for papillary thyroid carcinoma (PTC) and 2 cases suspicious for medullary thyroid carcinoma (MTC). In 110 cases suspicious for PTC, 106 were confirmed by the final surgical pathology. For other 4 cases, 1 case was atypical adenoma, 1 case was follicular thyroid carcinoma (FTC), and 2 cases were well differentiated tumor, uncertain malignant potential (WT-UMP). Diagnosis accuracy that reported as suspicious for PTC was 96.4%. 2 cases suspicious for MTC were confirmed by surgical pathology with accuracy as 100%. Diagnosis accuracy of SM group was 97.3%. 211 nodules were reported as “malignant, M” (210 PTCs and 1 case MTC). Among 210 cytological PTCs, 209 cases were confirmed by histology, and 1 case was confirmed to be atypical adenoma, the diagnosis accuracy of PTC was 99.5%. 1 cytological MTC was confirmed to be MTC with diagnosis accuracy as 100%. The diagnosis accuracy cytological M group was 99.5%. BRAFV600E mutation rate of SM and M were 82.3% and 95.5% respectively. 7 thyroid nodules were reported as “benign, B”. Among them, 3 cases were diagnosed as nodular goiters, 2 cases were follicular tumors and 2 cases were PTC diagnosed by histology. Overall, diagnosis accuracy for SM、M and B as a total was 98.2%. 23 thyroid nodules were reported as “atypia of undetermined significance, AUS” of which 19 cases were above TI-RADS 4B, the BRAFV600E mutation rate was 62.5%, and the final malignancy rate was 87%. We also found 10 “nondiagnostic, ND” cytology reports with the BRAFV600E mutation rate was 57.1%, and malignancy rate was 50%. Conclusion: The cytological diagnosis using SurePath-LBC for thyroid FNA is highly consistent with surgical pathological diagnosis specifically for PTC and MTC. The cytological diagnosis of B, AUS, and ND should be comprehensively handled by combining factors such as ultrasound characteristics, BRAFV600E mutation status, and nodule size. SurePath-liquid based cytology for thyroid FNA is highly accurate when the diagnosis of SM or M is made which is very important for further patient triage and the decision of reasonable surgical method.