The aim of the study was to investigate the efficacy and safety of minimally invasive segmentectomy in the treatment of lung cancer. A total of 86 lung cancer patients in early stage were selected for the treatment between May, 2010 and December, 2010. The patients were randomly divided into the control (n=43) and observation (n=43) groups. Patients in the control group received conventional thoracotomy as treatment, while thoracoscopic segmentectomy was performed for patients in the observation group. Factors including intraoperative bleeding amount, number of dissected lymph nodes, surgery duration, postoperative intubation time and length of stay (LOS) were compared between the two groups. A visual analogue scale was used for comparison of the postoperative incisional pain experienced by patients in the two groups. The incidence rate of postoperative complications of patients in the two groups was observed. We also assayed variations in the levels of serum inflammatory factors C-reaction protein (CRP), interleukin (IL) −6 and −10 of patients prior to operation and on the 3rd, 5th and 7th days and after operation via ELISA, and on the 7th day after operation, we determined the pulmonary function of patients. During the 5-year follow-up, the recurrence and survival rate of patients in the two groups were observed. In the observation group, the intraoperative bleeding amount of patients was significantly lower than that in the control group, and the surgery duration, postoperative intubation time and LOS were all shorter than those in the control group (P<0.05). By contrast, no significant difference was detected in a comparison of the number of dissected lymph nodes of patients between the two groups (P>0.05). Additionally, in the observation group, patients suffered less pain after operation than those in the control group (P<0.05), and on the 3rd, 5th and 7th days after operation, the levels of CRP, IL-6 and −10 in the observation group were significantly lower than those in the control group (P<0.05). After operation, the incidence rate of complications in the observation group was significantly lower than that in the control group (P<0.05), and the recovery in pulmonary function after operation was superior to that in the control group (P<0.05). In addition, the 5-year survival rate of patients in the observation group was significantly higher than that in the control group, and the recurrence rate was significantly lower than that in the control group (P<0.05). Minimally invasive segmentectomy shows better efficacy in the treatment of lung cancer at early stage than the conventional thoracotomy. In addition to the high safety during surgery, this technique can lower the incidence rate of postoperative complications, protect the pulmonary function, increase the survival rate and decrease the recurrence rate, which shows great value in clinical practice.