Thyroid cancer is the fifth communal cancer type in females. Latest data have demonstrated mir-125 is down-regulated in various cancer types. We conducted a case-control (179 cases, 165 controls) study in order to explore the association of mir-125 rs12976445 with the risk of thyroid cancer in Iranian population. rs12976445 C/T polymorphisms were investigated using PCR–RFLP. Logistic regression analyses were done to find the association of mir-125 rs12976445 C/T polymorphisms with thyroid cancer and its stages. The genotype frequencies for patients were [(TT: 81(45.2%), CT: 75(41.9%), CC: 23 (12.9%)], and for controls [(TT: 100 (60.1%), CT: 53(32.2%), CC: 12 (6.7%)]. The T allele distribution was significantly altered between patients and controls (P=0.002) with the odds ratio of 1.68. In the dominant model, there was a significant difference between CT vs TT genotypes (adjusted OR = 1.69, 95% CI= 1-2.8, P = 0.026), and between CC vs TT genotypes (adjusted OR = 2.18, 95% CI= 1-4.7, P = 0.047). We compared CT/CC genotype to TT genotype and found a highly significant difference (adjusted OR = 1.78, 95% CI= 1.15-2.74, P = 0. 0.009). Our findings suggest that miR-125a rs12976445 is a possible prognostic biomarker for thyroid cancer.