Objective To compare and analyze the effects of "double-microporous" three-port and traditional three-port thoracoscopic lobectomy on the levels of serum inflammatory factors in lung cancer patients. Methods A total of 80 lung cancer patients treated between January 2021 and January 2024 were retrospective collected and divided into the study group (n=41) and the control group (n=39) based on different surgical methods. The former underwent double microporous three hole thoracoscopic lobectomy, while the latter underwent traditional three hole thoracoscopic lobectomy. The surgical indicators and complications were compared between the two groups, as well as the lung function (maximum ventilation per minute, maximum expiratory flow), biochemical indicators (CYFRA21-1, LCN2, CA125), inflammatory factors (IL-6, IL-2R, IFN - γ) before and after surgery. Results Compared with the control group, the study group had a shorter chest tube placement time, hospitalization time, incision length, and operation time, and less blood loss and postoperative drainage (P<0.05). Compared with the control group, one week after surgery, the study group had higher maximum minute ventilation and maximum expiratory flow, and lower serum CYFRA21-1, LCN2, CA125, IL-6, IL-2R, and IFN-γ levels (P<0.05). There was no significant difference in the incidence of complications between the two groups (4.87% vs 7.69%) (P>0.05). Conclusion Compare with traditional three-port thoracoscopic lobectomy, "double-microport" three-port thoracoscopic lobectomy can promote lung function recovery, reduce biochemical indicators, alleviate inflammatory response, and accelerate patient recovery.