This study demonstrates a strong association of high urinary iodine with thyroid nodules and papillary thyroid cancer as well as aggressive cancer features, suggesting that high urinary iodine is a risk factor for thyroid cancer. The risk of high iodine intake for thyroid cancer has been suggested but not established. The objective of the study was to evaluate the relationship between urine iodine levels and thyroid nodule and thyroid cancer. We preoperatively tested fasting urine iodine in 154 thyroid nodule patients and correlated the results with pathological diagnoses and compared with 306 subjects as normal control. The median urine iodine (MUI) was 331.33 μg/L in patients with benign thyroid nodules versus 466.23 μg/L in patients with papillary thyroid cancer (PTC) (P=0.003), both of which were in the excessive iodine state and higher than the MUI of 174.30 μg/L in the control group (P < 0.001), which was in the sufficient iodine state. Excessive iodine state (MUI>300 μg/L) was seen in 62.75% of patients with benign thyroid nodules and 66.99% of patients with PTC, both of which were significantly higher than the iodine excessive rate of 19.93% in the control group (P<0.001). Moreover, MUI in patients with PTC with lymph node metastasis was significantly higher than that of PTC patients without lymph node metastasis (P<0.001). Urine iodine of thyroid cancer patients with stage III and IV disease was significantly higher than that of patients with stage I and II diseases (P<0.001). Multivariable analyses showed that, like sand calcification of thyroid nodule and TSH, urine iodine was an independent risk factor for PTC. These data demonstrate a significant association between high urinary iodine and benign and malignant thyroid nodules and PTC aggressiveness, supporting high urinary iodine as a risk factor for thyroid malignancy. Further studies are warranted to confirm these findings.