Objective To observe the therapeutic effect of subxiphoid uniportal video-assisted thoracoscopic anatomic pulmonary segmentectomy in the treatment of the early malignant lung tumors and localized benign lung lesions. Methods A retrospective analysis was conducted on the clinical data of 220 patients with early malignant lung tumors or localized benign lung lesions undergoing subxiphoid uniportal video-assisted thoracoscopic anatomic pulmonary segmentectomy in the Shanghai Pulmonary Hospital of Tongji University between Sep. 2014 to Apr. 2017. Follow-up after operation was performed regularly to evaluate incision pain and surgical outcome. Results The average age of 220 patients was (56.34±10.66) years, and 68 cases (30.91%) were males and 152 cases (69.09%) were females. The average operation time was (2.07±0.72) h, the average perioperative blood loss was (91.64±94.20) mL, and the average postoperative hospital stay was (4.64±9.97) d. A total of 14 patients underwent surgical conversion during the operation. Among them, 7 cases (3.18%, 7/220) had additional intercostal auxiliary hole during operation, 3 (1.36%, 3/220) were converted to subxiphoid uniportal video-assisted thoracoscopic lobectomy due to iatrogenic vascular or bronchial injury, and 4 cases (1.82%, 4/220) were converted to thoracotomy. The incidence of major complication (bleeding) was 0.45% (1/220). No patients suffered from bronchopleural fistula or developed incisional hernia. There were no perioperative deaths, with a postoperative 30 d survival rate of 100.00%. A total of 227 lesions were resected in 220 patients, 183 (80.62%) were malignant and the rest were benign or precancerous lesions. The median follow-up time was 30 months. No postoperative intractable incision pain occurred. Only 2 patients had itching of incision and surrounding skin, and 1 patient had hyposensation of incision and surrounding skin. No recurrence or metastasis occurred in patients with malignant tumors. Conclusion Subxiphoid uniportal video-assisted thoracoscopic anatomic pulmonary segmentectomy is an effective method for early malignant tumors and localized benign lesions. It can alleviate postoperative incision pain and has satisfactory therapeutic effects.