Traditionally, up to six incisions are required for video-assisted thoracoscopic surgery (VATS) for bilateral lung tumor resection. Besides, change posture was required during operation. In this case report, a single-incision subxiphoid approach was used for VATS to shorten operation time and reduce postoperative pain; this approach may also lead to better cosmetic results. However, in the described case, after a right-side tumor was removed, an episode of desaturation due to right-side tension pneumothorax was observed during one-lung ventilation for left lung tumor resection. CO2 insufflation was ceased, and the patient's condition improved. A literature review and suggestions for future similar surgeries are discussed.