ObjectiveTo analyze the results and rationality of the lesion-focused strategy with subsegment as the pulmonary anatomical unit for pulmonary nodules with a diameter of ≤2 cm which require surgery. MethodsClinical data of 246 patients with pulmonary nodules who underwent surgery in the Department of Thoracic Surgery of The First Affiliated Hospital of Nanjing Medical University from January 2017 to October 2018 were retrospectively analyzed, including 76 males and 170 females, with an average age of 53.30±11.82 years. The patients were divided into four groups, a single segmentectomy group, a segmentectomy combined with adjacent subsegmentectomy group, a single subsegmentectomy group and a combined subsegmentectomy group, according to the different surgical approaches, to compare preoperative, intraoperative, and postoperative related data. ResultsThere was no perioperative death. Among the four groups, there was no statistical difference in gender (P=0.163), age (P=0.691), diameter of the nodule (P=0.743), longitudinal position of the nodule (depth ratio, P=0.831), postoperative pulmonary leakage (P=0.752), intraoperative blood loss (P=0.135), pathological type (P=0.951) or TNM stage (P=0.995); there were statistical differences in transverse position of the nodule (P<0.001) and number of subsegments involved (P<0.001). The results of multivariate logistic regression analysis showed that compared with combined subsegmentectomy, the odds ratio (OR) of the lung nodule in segmentectomy combined with adjacent subsegmentectomy as intersegment nodules was 5.759 (95%CI 1.162 to 28.539, P=0.032).Conclusion The surgical strategy of lesion focused and subsegment as anatomical unit is safe and feasible for surgical treatment of pulmonary nodules with diameter ≤2 cm. The transverse position of the nodules is an important factor affecting the choice of surgical method for the middle and lateral nodules with a diameter of ≤2 cm, and the longitudinal location of the nodule is not an influencing factor. For nodules in inner zone, the diameter also is one of the factors influencing the choice of surgical method.