This study was conducted to evaluate the safety and effectiveness of localized lung resection combined with neoadjuvant chemotherapy in the treatment of stage I–II non-small cell lung cancer (NSCLC). A total of 88 patients, who were admitted to our hospital for first diagnosis and treatment, were selected. The patients were divided into control group (n=40 cases) and observation group (n=48 cases) according to the last digit of the admission number. The control group was treated with minimally invasive localized lung resection by thoracoscope. The observation group underwent the same procedure combined with two cycles of systemic neoadjuvant chemotherapy before the surgery was adopted in the observation group. The effects of both treatments were compared. The operation time, intraoperative blood loss and postoperative drainage volume of observation group were significantly lower than those of the control group (P<0.05). The surgical resection rate and margin negative rate of observation group were higher than those of control group, while the occurrence rate of complications was lower than that of control group; results were statistically significant (P<0.05). The serum neutrophil gelatinase associated lipocalin (lipocalin-2/NGAL), matrix metalloproteinase-9 (MMP-9) and carcinoembryonic antigen (CEA) levels of two groups after the treatment were lower than those before; however, levels in the observation group exhibited a distinct decrease. The difference has statistical significance (P<0.05). The follow-up time of two groups was 3–38 months and the median time was 20.5 months. The tumor survival period of observation group was not prolonged, however, the survival rate and quality rate of life were enhanced; the difference has statistical significance (P<0.05). Localized lung resection combined with neoadjuvant chemotherapy can effectively improve the surgical effect of stage I–II NSCLC, prolong the survival period, enhance the survival rate, decrease the occurrence rate of complications and reduce the tumor related factors lipocalin-2, MMP-9 and CEA levels.