Objective To investigate the effect of thoracoscopic lobectomy (PLT) in the treatment of non-small cell lung cancer (NSCLC) and the effects of interleukin-6 (IL-6), interleukin-10 (IL-10), hypersensitive C-reactive protein (hs-CRP) and stress levels. Methods A total of 138 NSCLC patients who received surgical treatment in Central Hospital of Chaoyang City from February to November 2020 were selected as the research subjects, and were divided into observation group and control group according to random number table method, with 69 cases in each group. The observation group was treated with PLT, and the control group was treated with traditional thoracotomy. The treatment effect, IL-6,IL-10, hs-CRP and stress index levels before and 5 d after surgery were compared between the two groups. Results The duration of operation and hospital stay in the observation group were shorter than those in the control group, the differences were statistically significant (P<0.05). The levels of IL-6, IL-10 and hs-CRP in both groups were higher than before 5 days after operation, but the levels of IL-6, IL-10 and hs-CRP in observation group were lower than control group, the differences were statistically significant (P<0.05). The levels of substance P, growth hormone and cortisol 5 days after operation in both groups were higher than before treatment, but the levels of substance P, growth hormone and cortisol in observation group were lower than those in control group, the differences were statistically significant (P<0.05). Conclusion PLT operation is effective in treating NSCLC patients. It can also improve the inflammatory response and stress state of the body after operation, it′s worth promoting.