Objective To explore the effect of microRNA-205 (miR-205) expression on migration and invasion of human melanoma cell lines (A375 and A2058) and its related molecular mechanism. Methods The miR-205 over-expressed melanoma cells (miR-205 group) were constructed via transfecting A375 and A2058 cell lines with Lenti-miR-205, and the cells transfected with blank vector virus were taken as control group (NC group). The migration and invasion ability of the cells in two groups were detected by scratch assay and Transwell assay, respectively. The confocal laser scanning microscopy was employed to observe the cell morphology and the cell number and fluorescence intensity of the cells expressing E-cadherin protein. Western blotting was performed to detect the protein expressions of E-cadherin, Twist, intergrin, vimentin, Zeb1, matrix metalloproteinase (MMP)-2 and MMP-9. Results At 8 h and 24 h of cells culture, the migration ability of A375 and A2058 cells in miR-205 group was significantly higher than that in NC group (P<0.01); the invasion ability of two kinds of cells in miR-205 group was lower than that in NC group (P<0.01). A375 and A2058 cells over-expressing miR-205 were transformed from shuttle, stroma type to round and epidermal type. Compared with the NC group, the E-cadherin expression of the cells in miR-205 group was significantly increased (P<0.01) and the cell number and fluorescence intensity of the cells expressing E-cadherin was increased, while the protein expressions of Twist, intergrin, vimentin, Zeb1, MMP-2 and MMP-9 were significantly decreased (P<0.01). Conclusion MiR-205 can inhibit the migration and invasion abilities of melanoma cells by inducing E-cadherin expression and reversing epithelial-mesenchymal transition.