To evaluate the effect of the postoperative short-term quality of life between uniportal and three portal video-assisted thoracic surgery for radical lung cancer resection. The perioperative data and short-term quality of life of 120 patients received uniportal and three portal video-assisted thoracic surgery for radical lung cancer resection were analyzed from September to November 2017 at Department of Thoracic Surgery, the First Affiliated Hospital of University of Science and Technology of China. There were 64 male and 56 female patients aging of (62±10) years (ranging from 28 to 82 years). There were 60 cases received uniportal (uniportal group) and 60 cases received three portal video-assisted thoracic surgery (three-portal group). Quality of life by measurement of functional and symptom scales was assessed before surgery at baseline, and 1, 2, 4, and 8 weeks after the operation. The test, χ(2) test, Fisher exact test and Wilcoxon rank-sum test were used to compare the date between the 2 groups. Repeated measurement variance was used for comparison of the quality of life at different time points. There were no statistically significant differences in the clinicopathological features of the two groups (>0.05). Intraoperative bleeding volume ((92±85) ml . (131±91) ml, =2.387, =0.019), postoperative catheter time ((4.4±3.1) days . (6.0±3.9) days, =2.401, =0.018), and postoperative hospitalization time ((6.2±4.0) days . (8.3±4.6) days, =2.626, =0.010) in the patients with uniportal group were less than that in three-portal group. Preoperative functional areas, symptom areas and overall health scores were similar in the two group. The functional areas such as physical function, role function, emotional function and social function and overall health status of uniportal group were significantly higher than those of three-portal group in postoperative time, while the fatigue and pain of uniportal group were significantly lower than that of three-portal group. Uniportal video-assisted thoracic surgery can achieve the same safety and radical of three-portal video-assisted thoracic surgery. It has advantages in intraoperative bleeding volume, postoperative time after operation, hospitalization time and postoperative life quality.