Background and Objectives Inflammation has been implicated in the initiation and progression of thyroid cancer. Neutrophil-to-lymphocyte ratio (NLR) is a simple index of systemic inflammatory response, and has been shown to be a prognostic indicator in some types of cancer. The aim of this study was to examine the relationship between NLR and clinicopathological features in patients with differentiated thyroid cancer. Methods Total white blood cell and differential counts of 159 patients with differentiated thyroid cancer were compared to those of 318 age- and sex-matched controls undergoing thyroidectomy for benign thyroid nodules. Clinicopathological variables, stratified by NLR tertiles, were analyzed. Results There was no difference in NLR between patients having benign and malignant thyroid nodules (P = 0.293). Cancer patients in the higher NLR tertile had significantly larger tumor size (P = 0.004). Higher NLR was observed in patients with high American Thyroid Association (ATA) risk of recurrence. Conclusions High preoperative NLR was associated with increased tumor size and high ATA risk of recurrence in patients with differentiated thyroid cancer.