Objective To investigate the advantage of the concept of wide exposure in uniportal video-assisted thoracoscopic surgery (uniportal-VATS) for radical resection of lung cancer and assess its safety and feasibility. Methods Clinical data of 255 patients (110 males and 145 females, a mean age of 54.3±7.9 years) with non-small cell lung cancer (NSCLC) who received wide exposure in uniportal-VATS or three portal VATS (3P-VATS) during August 2017 to March 2018 were retrospectively analyzed. There were 153 patients (67 males and 86 females, a mean age of 56.1±8.5 years) in the uniportal-VATS group and 102 patients (43 males and 59 femals, a mean age of 54.4±7.4 years) in the 3P-VATS group. The clinical effects were compared between the two groups. Results There was no statistical difference in the operation time between the uniportal-VATS and 3P-VATS (135.0±45.6 min vs. 142.0±39.5 min, P>0.05). The overall number of dissected stations (6.9±1.0) and LNs (14.5±3.0) in the uniportal-VATS group were similar with those in the 3P-VATS group (7.1±1.0, 15.1±1.7). The dissected stations of N2 LNs (uniportal-VATS: 4.1±1.7, 3P-VATS: 3.9±0.8) and number of dissected N2 LNs (uniportal-VATS: 8.0±0.9, 3P-VATS: 7.8±1.1) were both similar between the two groups. The duration of postoperative tube drainage and postoperative hospital stay of uniportal-VATS group (3.5±1.8 d and 7.2±0.9 d) were much shorter than those of 3P-VATS group (4.0±1.3 d and 8.8±2.0 d). No significant difference was found in incidence of postoperative complication between the two groups except that the incidence of subcutaneous emphysema in the uniportal-VATS group was much lower. There was no perioperative death in the two groups. Conclusion The concept of wide exposure in uniportal-VATS can meet the requirment of radical resection and it is a safe and valid method which can be used for radical resection of lung cancer.