<p>Keloids are a severe type of pathological scars caused by excessive connective tissue hyperplasia after skin injury. Uncontrolled angiogenesis during wound healing can contribute to keloid formation, highlighting the importance of angiogenesis regulation in keloid prevention and treatment. In this study, angiogenesis-related biomarkers in keloids were identified using a combination of machine learning methods and weighted gene co-expression network analysis (WGCNA), based on gene expression data from the Gene Expression Omnibus (GEO) database. <i>Neuropilin-1</i> (<i>NRP1</i>) was selected for further investigation and validated in clinical tissue samples using immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Immune microenvironment analysis indicated a significant positive correlation between the <i>NRP1</i> expression level and the abundance of immune and stromal cells, particularly endothelial cells. The biological role of <i>NRP1</i> at the single-cell level revealed that keloid endothelial cells potentially promote collagen deposition in the extracellular matrix (ECM), which is closely associated with the keloid NRP1⁺ endothelial cells. In summary, <i>NRP1</i> plays an essential role in the occurrence and development of keloids and represents a promising angiogenesis-related therapeutic target.</p>