The aim of the present study was to explore the feasibility, safety and effectiveness of complete endoscopic radical resection of thyroid cancer via an oral vestibule approach. A total of 60 patients with unilateral thyroid papillary carcinoma were divided into two groups. Half of them underwent complete endoscopic surgeries via an oral vestibule approach at the Department of Head and Neck Surgery of Fujian Cancer Hospital between November 2014 and December 2016. The other 30 patients underwent traditional open surgeries. All the patients underwent unilateral lobectomy and central neck dissection. Tumor diameter, surgery duration, intraoperative inflation pressure and end-tidal CO2 flow rate, intraoperative peak value of the partial pressure of end-tidal CO2, postoperative extubation time, the number of lymph nodes in the specimens of central neck dissection and postoperative complications were noted. From this data, tumor diameter (T stage of tumor), surgery duration, postoperative extubation time, the number of lymph nodes in the specimens of central neck dissection and postoperative complications were compared between the two groups. In the endoscopic group, 1 patient had a tracheal injury, and 1 patient had a submental skin perforation. Furthermore, 17 patients experienced transient numbness of the lower lip, 5 patients experienced an abnormal increase in the partial pressure of end-tidal CO2, and 2 patients experienced postoperative headache. No recurrent laryngeal nerve injury, postoperative bleeding, or infection was determined. There were no significant differences in all items of the indexes, compared with those patients who underwent open radical surgery. The lymph nodes from region VI may be well exposed and completely removed through this novel procedure with no visible scars, which not only ensured the surgery criterion was met, but also met the cosmetic requirements of the patients. The present study conducted procedures safely by surgeons highly skilled in performing laparoscopic surgery.