Objective: we aim to investigate the effect of the size of the nodules on the diagnostic efficiency of fine-needle aspiration biopsy (US-FNAB) by using ultrasound-guided guided percutaneous fine-needle aspiration biopsy (Thyroid nodule) with TI-RADS Grade ≥ 4. The purpose of this study is to provide some guidance for the selection of biopsy methods of suspicious malignant thyroid nodules. Materials and methods: 342 consecutive thyroid nodules from 332 patients between January 2017 and December 2018 were enrolled , the thyroid nodules are grouped according to largest diameter (group A, ≤5.0mm；group B, 5.1mm-10.0mm; group C，10.1mm-15.0mm; group D,15.1mm-20.0mm; group E，>20.0mm),US-FNAB results were compared with surgical pathological tissue sections and analyzed the diagnostic efficacy of US-FNAB results.RESULTS: The final surgical pathology confirmed that 254 nodules were malignant and 88 nodules were benign. Among the five groups A, B, C, Dand E , the sensitivity was 61.9%、76.6%、89.8%、72.4%、62.7%(p=0.010 ), specificity were 87.5%、 88.9%、78.9%、100.0%、91.2%(p=0.052) , and the accuracy was 69.0%、78.6%、87.2%、78.9%、74.1%(p=0.443), the positive predictive rates were 92.9%、97.3%、92.9%、100.0%、91.3%%( p=0.721), and the negative predictive rates were 46.7%、42.1%、71.4%、52.9%、62.0%(p= 0.120) . The malignant rates were 81.6%、83.9%、75.6%、76.3%、60.0%（p=0.005）. Conclusion: In all groups, The sensitivity of Group C (10.1 mm-15.0 mm) was higher than that of other groups , in Group A (≤5 mm) and Group E (＞20.0 mm) had lower Thyroid nodule sensitivity than other groups. However, there were no significant differences in specificity, positive predictive value and accuracy among groups. Therefore, we suggest that US-FNAB should be repeated at intervals for small nodules less than 5mm, the CNB (core needle biosy) is feasible for nodules > 20.0 mm, and US-FNAB should be the first choice for nodules less than 10.1 mm-15.0 mm.