INTRODUCTION: Skin aging is a complex, multifactorial process involving cellular damage, inflammation, and increased susceptibility to diseases. Despite its importance, the role of SPRY1 in skin aging remains poorly understood. This study aims to investigate the function of SPRY1 in skin aging, particularly its impact on macrophage M1 polarization, and explore its potential as a therapeutic target for mitigating skin aging and melanoma. METHODS: Bioinformatics analyses were performed using datasets from the GTEx and GEO databases, alongside in vitro cellular experiments. These included Weighted Gene Co-expression Network Analysis (WGCNA), single-cell sequencing, and various cellular assays in RAW264.7 murine monocyte/macrophage leukemia cells and NIH/3T3 mouse skin fibroblasts. The assays comprised gene transfection, Cell Counting Kit-8 (CCK-8) assays, quantitative real-time PCR (qRT-PCR), and measurements of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity. RESULTS: SPRY1 was identified as a key gene within modules linked to skin aging. Single-cell sequencing revealed its enrichment in macrophages and keratinocytes. Knockdown of SPRY1 in RAW264.7 cells resulted in a shift from M1 to M2 macrophage polarization, reduced oxidative stress, and decreased expression of inflammatory markers. In NIH/3T3 cells, SPRY1 knockdown reduced cell viability and lowered the expression of inflammatory genes. Additionally, SPRY1 expression was downregulated in melanoma, and its reduced levels were associated with poorer survival outcomes. CONCLUSIONS: SPRY1 accelerates skin aging by promoting macrophage M1 polarization and may serve as a promising therapeutic target. Future research should focus on in vivo validation and further exploration of its regulatory networks to develop novel treatments.