As an aggressive skin cancer with high morbidity and mortality, melanoma is becoming a heavy burden on society. This study is aimed to identify genes associated with melanoma. Both expression profile of GSE31909 and methylation profile of GSE53801 were downloaded from Gene Expression Omnibus. GSE31909 included 3 melanoma cell line SK-MEL-28 samples, 3 melanoma cell line LOXIMVI samples, 3 normal melanocyte line HEMn samples and 3 normalmelanocyte line HEMa samples. Meanwhile, GSE53801 included 2 humanmelanoma cell lines and 8 normal human epidermal melanocytes. Differentially expressed genes (DEGs) and differentially methylated sites were screened using limma package in R. Besides, common genes of the DEGs and the genes with differentially methylated sites were identified. Afterwards, enrichment analyses were performed for the DEGs and the common genes using DAVID online tool and the cytoscape plug-in clueGO + cluePedia, respectively. Moreover, transcription factor (TF)-mRNA pairs were searched and then TF-mRNA regulatory network was visualized by Cytoscape. Additionally, the DEGs were validated in melanoma cell lines A375 samples from GSE68453. Total 609 DEGs and 5893 differentially methylated sites in melanoma cell lines compared with normal melanocytes were screened. And 140 common genes (e. g. CTGF, PLXNB1, CD9, ADM and EPHA4) were identified. Several functions were enriched, including response to wounding and integrin binding. Meanwhile, the TF-mRNA regulatory network involved several transcription factors and their target genes (e. g. LDOC1, CTGF, STAT3, EGR1, SETDB1 and C-MYC), which might function through interacting with each other (e. g. STAT3. CTGF). These genes might play important roles in melanoma progression. (C) 2016 Elsevier Inc. All rights reserved.