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• EAF2 plays a key role in human malignancies. • EAF2 expression was closely associated with the immune-infiltrating levels of immune cells. • EAF2 has a strong positive correlation with CD19, implying they may be functional partners in the immune response of SKCM. • EAF2 could be a promising and potential biomarkers for the diagnosis and immunotherapy in patients with melanoma. Skin cutaneous melanoma (SKCM) accounts for over 75% of skin cancer-related deaths each year. EAF2, as a member of EAF family, has been found in several cancers, however, the role of EAF2 in SKCM is rarely studied. In this study, we utilized multiple bioinformatics tools to systematically analyze the expression of EAF family and investigate the prognostic value of EAF2 in melanoma. We found both transcriptional and proteomics expression expressions of EAF2 were elevated in SKCM. Survival analysis and ROC curves showed significant diagnostic and prognostic ability of EAF2. Importantly, EAF2 expression was closely associated with the immune-infiltrating levels of B cells, CD4+ T, CD8+ T, neutrophils, macrophages and dendritic cells. Co-expression analysis showed EAF2 has a strong positive correlation with CD19, implying they may be functional partners in the immune response of SKCM. In summary, our study is the first to reveal that increased expression of EAF2 is significantly correlated with tumor progression and better prognosis in SKCM patients. The role of EAF2 in SKCM demonstrated that it might be a potential and promising biomarker for the diagnosis and prediction of prognosis in patients with SKCM. [ABSTRACT FROM AUTHOR]