Objective To introduce the surgical and perioperative strategy for giant mediastinal mass. Methods The clinical data of 21 patients with giant mediastinal mass who underwent surgical treatment in Xinhua Hospital of Shanghai from January 2007 to July 2016 were retrospectively reviewed. There were 14 males and 7 females, with a mean age of 34.62 ± 22.95 years (range: 11 months to 79 years), and mean weight of 58.07±22.24 kg (range: 10.8 to 90.5 kg). Their clinical manifestation, anesthesia methods, surgical treatment and the prognosis were analyzed. Results The tumor volume ranged from 8 cm×6 cm×6 cm to 25 cm×25 cm×8 cm. For surgical approach, 12 patients received median sternotomy, 5 anterior lateral incision, 1 posterior lateral incision, 2 "L"-shape sternotomy, 1 cervical and thoracic "]"-shape incision. All patients were given mass radical resection, except one patient with two-stage resection. Twelve patients needed other tissues resection besides the single tomor resection. The operation time was 55-480 (207.86±87.67) min, blood loss volume 700 (10-4 000) ml, intraoperative blood transfusion 800 (0-4 100) ml, postoperative mechanical ventilation time 4.75 (0-87) h, postoperative drainage time 3-12 (7.43±2.66) d, the total drainage volume 295-4 940 (1 584.76±1 173.98) ml, average daily drainage volume 62-494 (204.90±105.76) ml, and postoperative hospital stay 7-47 (11.86±8.51) d. The postoperative complications included pericardial effusion in 1 patient, Horner syndrome in 1, left recurrent laryngeal nerve injury with the left phrenic nerve injury in 1, right phrenic nerve injury in 1 and delayed wound healing in 1. The remaining patients recovered well. All patients were followed up for 1 month to 9 years. Till September 1, 2016, 5 patients died and 2 suffered recurrent tumor. Conclusion It is safe to perform surgical treatment after comprehensive evaluation of patients with giant mediastinal mass, perioperative mortality is low, and prognosis in patients with benign tumor is good.