OBJECTIVE: Melanoma is one of the most aggressive and fatal forms of skin cancer. MicroRNAs (miRNAs), a series of small noncoding RNAs, function through translation repression and/or mRNA degradation. In the present study we aimed to explore the potential role and underlying mechanism of miR-138 in the regulation of melanoma development. STUDY DESIGN: We suggested that miR-138 expression was strongly upregulated in melanoma tissues and human melanoma cells by comparison with their corresponding controls. RESULTS: Specific overexpression of miR-138-5p promoted Me45 melanoma cell proliferation. By contrast, specific knockdown of miR-138 prevented its proliferation. Bioinformatics analysis indicated that miR-138-5p potentially targets the 3’-untranslated region (3’-UTR) of human telomerase reverse transcriptase (hTERT), which was confirmed by luciferase activity assay. Further, this study revealed that miR-138-5p regulated the proliferation of human melanoma cells by directly regulating hTERT expression as shown by the result that knockdown of hTERT reversed the promotive effects of miR-138-5p on proliferation of human melanoma cells. CONCLUSION: Taking all these results together, this study demonstrated that miR-138-5p acts as a carcinogenesis factor by targeting hTERT during human melanoma development. (Anal Quant Cytopathol Hist-pathol 2019;41:39–46). © Science Printers and Publishers, Inc.