Objective To investigate the application effect of pentazocine in single port thoracoscopic radical resection of lung cancer. Methods A total of 110 patients with stageⅠ-Ⅱnon-small cell lung cancer admitted to First People’s Hospital of Jiujiang from December 2020 to March 2022 were selected and divided into conventional group and combined group according to the random number table method, with 55 cases in each group. Patients in conventional group were treated with single port thoracoscopic radical resection of lung cancer, while patients in combined group were treated with pentazocine combined with single port thoracoscopic radical resection of lung cancer. The visual analogue scale (VAS) score, malondialdehyde (MDA), and superoxide dismutase (SOD), CD3+, CD4+, CD8+, CD4+/CD8+ levels and adverse reactions were compared between the two groups. Results The VAS scores at 1h, 6h and 12h after operation in combined group were significantly lower than those in conventional group (P＜0.05). The levels of MDA and SOD in two groups at three days after operation were significantly higher than those at one day before operation (P＜0.05), and MDA level of the combined group was significantly lower than that of conventional group (P＜0.05), SOD level was significantly higher than that of the conventional group (P＜0.05). At 1 day and 7 days after operation, CD3+, CD4+, CD8+ and CD4+/CD8+ in combined group were significantly higher than those in conventional group (P＜0.05). There was no significant difference in the incidence of total adverse reactions between the two groups (P＞0.05). Conclusion Pentazocine combined with single port thoracoscopic radical resection of lung cancer in the treatment of stageⅠ-Ⅱnon-small cell lung cancer can effectively relieve postoperative pain, reduce oxidative stress reaction, improve patients’ immunity, with good safety, and can be promoted in clinical practice.