Background Papillary thyroid cancer (PTC) is the most frequent endocrine cancer. Aberrant expression of miRNAs can increase the risk of thyroid cancer. We aimed to investigate the miR-126-3p and miR-146a-5p plasma levels in patients with thyroid nodules and to identify their associations with clinicopathological characteristics, and progression of PTC. Methods: We enrolled 40 healthy control and forty patients with thyroid nodules; benign thyroid nodules (BTN), (n=30), and PTC(n=10). We analyzed miR-126-3p and miR-146a-5p levels by using real-time PCR. Results: miR-126-3p expression level was downregulated in PTC patients (0.40±0.11) compared with BTN (0.58±0.12) and healthy subjects (0.87±0.31), P<0.001*Regarding miR-146a-5p, its level was upregulated in PTC patients (4.59±1.61) compared with BTN (3.77±0.96) and healthy subjects (0.99±0.41), Additionally, miR-126-3p and miR-146b-5p levels were significantly associated with tumor progression, lymph node metastasis, TNM staging, and thyroid function tests. The diagnostic power of miR-126-3p in the prediction of PTC, the AUC was 0.860 with a sensitivity of 60 % and specificity of 87.3% at cutoff values =0.49. miR-146a-5p level in the prediction of PTC, the AUC was 0.742 with a sensitivity of 80 % and specificity of 74.3% at cutoff values =3.4.