Objective To compare the effect of uniportal and multiportal thoracoscopic lobectomy, and to explore the advantages and applications of uniportal thoracoscopic lobectomy in enhanced recovery after surgery. Methods Totally 169 patients with video-assisted thoracoscopic lobectomy in Department of Thoracic Surgery of Sichuan Cancer Hospital from January to December 2016 were enrolled. There were 99 males and 70 females with age of 60.83±7.24 years. Patients were divided into two groups: a uniportal group (78 patients) and a multiportal group (91 patients) . Patients’ clinical and pathological materials were collected. Postoperative pain, complications and hospital stay, etc of the two groups were compared. Results All patients were successfully discharged without serious postoperative complication or death. Patients in the multiportal group had smaller surgical incisions than that in the uniportal group (3.12±0.73 cm vs. 6.38±1.50 cm, P=0.016). Pain scores at postoperative 24 and 48 hours of the uniportal group were less than those of multiportal group (4.18±1.67 vs. 6.54±1.83, 3.05±1.47 vs. 4.68±1.64, P<0.05). Operation data, postoperative complications and hospital stay were similar in both groups. Conclusion Uniportal video-assisted thoracoscopic lobectomy makes smaller incisions and can further reduce postoperative pain and dosage of morphine. The operation is safe and worthy of wide application in enhanced recoveryafter surgery.