Objective: To evaluate the clinical effects of unilateral thyroidectomy with thyroid isthmectomy in the treatment of papillary thyroid carcinoma. Methods: 107 patients with papillary thyroid carcinoma with maximum diameter≤1 cm were classified into control group (n=37, total thyroidectomy) and study group (n=70, unilateral thyroidectomy plus isthmectomy) based on surgical methods. The safety indicators (surgery time, intraoperative blood loss, permanent recurrent laryngeal nerve injury rate, incidence of permanent hypoparathyroidism), serological indicators [thyroglobulin (Tg) antibody, serum thyroglobulin, serum calcium and parathyroid hormone (PTH) levels], postoperative complications and TSH suppression treatment compliance rate and average daily maintenance dose of levothyroxine at 6 months after surgery were compared between the two groups. Results: Compared with the control group, the study group had slightly longer surgical time and less intraoperative blood loss volume (P<0.05), and the permanent recurrent laryngeal nerve injury rate and incidence rate of permanent hypoparathyroidism were reduced (P<0.05). The overall incidence rate of postoperative complications in the study group was lower compared to the control group (P<0.05). The Tg antibody, thyroglobulin, serum calcium and PTH levels in the study group at 1 month after surgery were better than those in control group (P<0.05), and the TSH suppression treatment compliance rate at 6 months after surgery was higher, and the required average daily maintenance dose of levothyroxine was less (P<0.05). Conclusion: For papillary thyroid carcinoma with maximum diameter≤1 cm, unilateral thyroidectomy combined with isthmectomy can protect parathyroid function and recurrent laryngeal nerve function while ensuring the radical effect of tumor, and reduce complications, thus it is a better surgical choice.