Abstract: Background　Lung cancer is the leading cause of cancer-related deaths worldwide, and its evolutionary molecular mechanisms and the heterogeneity of the tumor microenvironment remain to be further elucidated. Lung adenocarcinoma progresses gradually from precancerous lesions to invasive adenocarcinoma. Multiple primary lung cancers can serve as an ideal in vivo model, enabling the analysis of the entire process of tumor evolution while eliminating the interference of individual differences to a certain extent. Objective　This study aims to take multiple primary lung cancer as a model, adopt single-cell transcriptome sequencing technology to systematically map the single-cell atlases of paracancerous tissues and distal normal lung tissues corresponding to atypical adenomatous hyperplasia, minimally invasive adenocarcinoma and invasive adenocarcinoma, analyze the gene expression alterations of paracancerous tissues during the progression of lung adenocarcinoma, so as to offer a new perspective for researches on the progression mechanism of lung adenocarcinoma.Methods　In this study, 11 samples (7 paracancerous tissue samples and 4 distal normal lung tissue samples) were obtained via surgery for single-cell transcriptome sequencing. Cell clustering and annotation, screening of differentially expressed genes using the Wilcoxon rank-sum test, and cell-cell interaction analysis with CellPhoneDB were performed sequentially. A P value less than 0.05 was considered statistically significant. Results　A total of 205, 154 valid single cells were obtained, and 9 major cell types were identified. It was found that the cellular composition of paracancerous tissues undergoes staged remodeling as lesions progress. Specifically, the proportion of AT2 cells abnormally surged to nearly 100% at the AAH stage, then decreased at the MIA stage alongside an elevated percentage of airway epithelial cells. The numbers of differentially expressed genes in AT2 cells within paracancerous tissues at the AAH, MIA and IA stages were 2150, 416 and 339 respectively. Intercellular interaction analysis revealed that communication between fibroblasts and endothelial cells continuously intensified starting from the AAH stage, forming a core hub that fosters a pro-tumor microenvironment. Paracancerous tissues serve as a critical functional microenvironment for the early progression of lung adenocarcinoma, with aberrant activation of AT2 cells, disrupted immunosuppression, and stromal cell-dominated communication networks acting as its core regulatory mechanisms. Conclusion　The paracancerous microenvironment is not merely a passive secondary alteration following tumorigenesis; it may actively participate in regulating the early malignant transformation process of lung adenocarcinoma.