Objective To evaluate the feasibility and safety of modified gasless endoscopic thyroidectomy via the subclavian approach for differentiated thyroid carcinoma. Methods A retrospective analysis was conducted on the clinical data of 53 patients with unilateral differentiated thyroid carcinoma (cTNM stage≤T1) who underwent surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Xiangtan First People’s Hospital from January 2023 to December 2023. All patients were divided into three groups: open thyroidectomy (open group, n=22), conventional subclavian endoscopic thyroidectomy approach(C-SETA group, n=18), and modified subclavian endoscopic thyroidectomy approach (M-SETA group, n=13). It was recorded and compared for the operation time, hospital stay, number of central lymph node dissections, postoperative complications and hospitalization costs of the three groups. The follow-up was conducted at the outpatient clinic from one month post-operation to January 2025. The quality of life was evaluated using the thyroid cancer-specific quality of life questionnaire. Results There were statistically significant differences in terms of operative time, length of hospital stay, number of central lymph node dissections, and quality of life scores among the three groups of patients (P<0.05). However, the hospitalization costs showed no statistically significant difference among the three groups of patients (P>0.05). The postoperative comparison showed that the operation time of both the laparoscopic groups was significantly longer than that of the open group (P<0.05), and there was no significant difference between the two endoscopic groups (P>0.05). The postoperative hospital stay of the endoscopic group was significantly shorter than that of the open group. The obtained number of lymph nodes was significantly higher in the endoscopic group than that in the open group. Furthermore, the scores of quality of life were significantly better in the endoscopic group than that in the open group (P<0.05). No postoperative complications (recurrent laryngeal nerve injury, superior laryngeal nerve injury，hypoparathyroidism, wound infection, hemorrhage) or tumor recurrence/metastasis occurred in any group during follow-up. Conclusions The modified gasless endoscopic thyroidectomy trans-subclavian approach (M-SETA) is a feasible and safe technique for treating differentiated thyroid carcinoma. The operation time is longer than that of open surgery, but it is comparable to the traditional axillary approach. M-SETA does not increase the risk of postoperative complications, achieves more lymph nodes thorough central compartment dissection (≥compared to the open group).This surgical procedure has a concealed incision, offering cosmetic advantages and shortening the hospital stay. M-SETA does not significantly increase costs compared to open surgery, which provides significantly better postoperative quality of life.