Objective: To explore the application of area ratio method of ultrasound elastography in the differential diagnosis of benign and malignant thyroid nodules. Methods: This study retrospectively analyzed the data of 299 patients who underwent thyroid nodule resection in Zhuozhou Hospital between January 2019 and March 2021. All patients were subjected to ultrasound elastography at 1 week before operation, and relevant area ratios were calculated. The thyroid nodules were classified qualitatively according to ultrasound elastography classification. Ultrasound elastography grade 1 to grade 3 were defined as benign, and grade 4 to grade 5 were defined as malignant. The diagnostic results were compared with postoperative pathological results. Results: A total of 315 thyroid nodules were detected by gray-scale ultrasound in 299 patients. Pathological results showed 203 benign nodules and 112 malignant nodules. The area ratio of ultrasound elastography for benign nodules was 1.29±0.13, lower than that of malignant nodules (1.75±0.10; t=31.642, P<0.05). The diagnostic sensitivity, specificity and accuracy of preoperative ultrasound elastography classification were 53.57%, 98.03% and 82.22%, respectively. When the area ratio of ultrasound elastography ≥1.51 was defined as malignant and <1.51 was defined as benign, there were 205 benign nodules and 110 malignant nodules. The diagnostic sensitivity, specificity and accuracy of area ratio method of ultrasound elastography were 94.64%, 98.03% and 96.83%, respectively. The diagnostic efficiency of area ratio method of ultrasound elastography was better than ultrasound elasticity classification (Z=7.248, P<0.001). Conclusion: Area ratio method of ultrasound elastography is of high application value in clinical differential diagnosis of benign and malignant thyroid nodules.