Skp2 participates in the regulation of cell growth cycle and promotes the growth of tumor cells. It was speculated that miR-590-5p could regulate the expression of Skp2 and have therapeutic effects on malignant melanin. In this study, the expression of Skp2 was detected by qRT-PCR and Western blot (WB), and the targeted binding between miR-590-5p and Skp2 was verified by dual luciferase reporting assay. Subsequently, cell proliferation activity was detected by CCK8, cell invasion was detected by Transwell, and cell apoptosis was detected by mitochondrial membrane potential assay. The results indicate that Skp2 is highly expressed in melanoma cells and inhibits the proliferation and invasion of melanoma cells. However, miR-590-5p can bind to Skp2 in a targeted manner. miR-590-5p is underexpressed in melanoma cells, and its overexpression can inhibit Skp2 expression and proliferation and invasion of melanoma cells. Our results showed that miR-590-5p could inhibit melanoma cell development by targeting Skp2. This study provides more therapeutic targets for the treatment of melanoma.