Objective To explore the application value of endoscopic thyroidectomy through axillary or oral vestibular approaches in the treatment of unilateral papillary thyroid carcinoma with negative cervical lymph nodes （cN0 stage）. Methods A total of 86 patients with cN0 stage unilateral papillary thyroid carcinoma who underwent surgical treatment from January 2020 to June 2023 were randomly divided into a control group and an observation group, with 43 patients in each group. The control group underwent endoscopic thyroidectomy via the oral vestibular approach, while the observation group underwent endoscopic thyroidectomy via the axillary approach. The surgical time, intraoperative blood loss volume, postoperative drainage volume, number of central lymph node dissections, visual analog scale （VAS） score, total incidence of complications, and postoperative satisfaction were observed and compared between the two groups of patients. Results The intraoperative blood loss volume, postoperative drainage volume, and VAS score of the observation group were all lower than those of the control group （P<0.05）, but the number of central lymph node dissection was higher （P<0.05）. There was no statistically significant difference in surgical time and hospitalization time between the two groups of patients （P>0.05）. There was also no statistically significant difference in the total incidence of complications between the observation group （16.27%） and the control group （18.60%） （P>0.05）, but the postoperative satisfaction rate （97.67%） of the observation group was higher than that of the control group （79.07%）, and the difference was statistically significant （P<0.05）. Conclusion Transaxillary endoscopic thyroidectomy can better protect the anterior cervical functional area and reduce postoperative discomfort in the anterior neck. Comparably, transoral vestibular endoscopic thyroidectomy features smaller operating space, higher difficulty, overall longer surgical time, and higher risks of postoperative infection, despite better cosmetic effect. Therefore, transaxillary endoscopic thyroidectomy is more effective in the treatment of cN0 unilateral papillary thyroid carcinoma.