Objective To select microRNAs (miRNA) associated with human cutaneous malignant melanoma (MM). Methods Total RNA was extracted from 6 tissue samples of MM and 9 human control samples of pigmented nevi, and small RNAs of less than 200 bp were enriched, miRNA microarray was used to select differentially expressed miRNAs between tissue samples of MM and pigmented nevi from 468 candi-dates. The expression of differentially expressed miRNAs was confirmed by fluorescence based real-time quan-titative PCR (qPCR) in all of these samples. Those miRNAs that were identified as differentially expressed with both miRNA microarray and qPCR were considered as significant miRNAs. Results Between the tissue samples of MM and pigmented nevi, 12.18% to 86.33% of miRNAs differentially expressed by more than 2 folds, 1.28% to 19.02% by more than 5 folds, and 0.43% to 5.34% by more than 10 folds. The expression of miRNA-21 was obviously up-regulated, while that of miRNA-320 and miRNA-494 was down-regulated in the MM samples. Conclusion There is an increase in the expression of homo sapiens miRNA-21 but a decrease in that of miRNA-320 and miRNA-494 in MM tissues.