ObjectivesCongenital pulmonary airway malformation (CPAM) is a common fetal lung developmental abnormality whose pathological process is not fully understood.MethodSingle-cell sequencing technology is a novel high-throughput method that can reveal differences between different cell types and their role in disease.ResultsBy analyzing single-cell sequencing data from CPAM lesion tissue and normal tissue, we found an increase in erythrocytes, plasma cells and mast cells in CPAM samples. Additionally, genes such as CCL5, NKG7, GZMB, and SCGB1A1 were highly expressed in CPAM lesion tissues. The differentially expressed genes in CPAM samples are mainly related to functions such as inflammatory response, tissue remodeling, and immune response. Moreover, analysis of the signaling pathways involved in these differentially expressed genes revealed that pathways such as lysosome, phagosome, adherens junction, focal adhesion, and protein processing in the endoplasmic reticulum may be associated with the pathological process of CPAM.ConclusionThis study provides an in-depth analysis of the cellular differences between CPAM tissues and normal tissues using single-cell sequencing technology, revealing key cell types and functions involved in the development of CPAM. These findings provide important clues for a better understanding of the pathological process of CPAM and serve as a basis for identifying potential therapeutic targets.