Objective To discuss the safety, feasibility and advantages of tubeless trans-subxiphoid thoracoscopic surgery in anterior mediastinal tumor resection. Methods A total of 32 patients suffering anterior mediastinal tumor were enrolled, including 17 patients (8 males and 9 females) with average age of 31.8±8.4 years who had been performed tubeless trans-subxipohoid tharcoscopic surgery and 15 patients (8 males and 7 females) with average age of 31.1±9.2 years who had been performed traditional trans-subxipohoid tharcoscopic surgery. The differences of surgical duration, the lowest intraoperative arterial oxygen saturation (SaO2), postoperative awaking time, postoperative pain visual analogue score (VAS), postoperative pulmonary recruitment time, duration of postoperative hospital stay and hospitalization cost were analyzed. Results Postoperative awaking time (18.5±1.8 min vs. 28.9±4.2 min, P=0.000), postoperative VAS (1.6±0.6 vs. 3.5±7.4, P=0.000), duration of postoperative hospital stay (2.5±7.2 d vs. 4.3±1.1 d, P=0.000) and hospitalization cost (3.2±1.1 ten thousand RMB vs. 4.9±1.1 10 ten thousand RMB, P=0.000) in the tubeless group were better than those in the control group. There was no significant difference in surgical duration (51.7±6.5 min vs. 55.1±8.5 min), the lowest intraoperative SaO2 (98.5%±0.9% vs. 98.1%±0.8%), postoperative pulmonary recruitment time (33.9±12.2 d vs. 38.4±15.2 d, P>0.05) between the two groups.Conclusion Tubeless trans-subxiphoid thoracoscopic surgery is safe, feasible and advanced in anterior mediastinal tumor resection.