Objective To evaluate the relationship between AIM2 Inflammasome in lung tissue and ventilator-related lung injury in patients undergoing thoracoscopic lobectomy. Methods A total of 750 patients with ASA grade I or II, aged 40 to 80 years old, regardless of gender and weight 40 to 90kg, who intended to undergo thoracoscopic lung cancer surgery under elective general anesthesia were selected from the First Central Hospital of Baoding City and the Affiliated Hospital of Hebei University from September 2019 to December 2021. Lung tissue >8cm away from the lesion was taken during intraoperative lobectomy. Western blot assay was used to detect the expression of melanoma deficiency factor 2 (AIM2), apoptosis-associated microprotein (ASC) and the precursor of caspase -1 (pro-Caspase1). The diagnostic criteria proposed in the guidelines for Diagnosis and Treatment of acute lung injury/acute respiratory distress syndrome were used to determine the occurrence of single lung ventilation-related lung injury. According to the incidence of postoperative single lung ventilator-related lung injury, patients were divided into single lung ventilator-related lung injury group (group I) and single lung ventilator-related lung injury group (group NI). Logistic regression analysis was used to screen the risk factors of lung injury associated with single lung ventilation. ROC curve and precision recall curve (PR curve) were used to predict the accuracy of risk factors in diagnosing lung injury associated with single lung ventilation. Results A total of 678 patients undergoing thoracoscopic lung cancer surgery were included in this study. Postoperative pulmonary injury with single lung ventilation occurred in 115 patients (16.9%). There were significant differences in age, FEV1/FVC, single lung ventilation time, operation time, AIM2, ASC and pro-Caspase1 between the NI group and the I group (P<0.05). Multivariate Logistic regression analysis showed that age, FEV1/FVC, duration of single lung ventilation, AIM2, ASC and pro-Caspase1 were risk factors for lung injury during single lung ventilation, and the results of secondary sensitivity analysis showed that AIM2, ASC and pro-Caspase1 protein expression were still independent risk factors for lung injury after single-lung ventilation. ROC curve and PR curve showed that AIM2 inflammasome had high sensitivity and specificity in predicting the occurrence of lung injury related to single lung ventilation. Conclusion Increase AIM2 inflammasome in lung tissue is an independent risk factor for single-lung ventilator-related lung injury in patients undergoing thoracoscopic lobectomy and AIM2 inflammasome in lung tissue can accurately predict single-lung ventilator-associated lung injury