Objective To study the effect and mechanism of resveratrol on proliferation, migration and invasion of melanoma cells. Methods qRT-PCR was used to detect the expression of miR506 in melanoma cells after resveratrol treatment. miR506 inhibitor was transfected into melanoma cells and qRTPCR was used to detect the interference effect. Resveratrol reduced miR506 melanoma cells, MTT assay for cell proliferation. Colony forming assay was used to determine cell clone ability. Scratch healing test was used to determine migration. Cell invasion was measured in Transwell chamber. Western blot was used to detect the expression of MMP-2 and MMP-9 protein in cells. Results The expression level of miR-506 in resveratrol treated melanoma cells was upregulated. miR506 inhibitor significantly inhibited the expression of miR506 in cells. Resveratrol can significantly reduce the proliferation, clone, migration and invasion of melanoma cells. Compared with cells treated with resveratrol alone, the expression of MMP-2, MMP-9 and proliferation, cloning, invasion, migration of melanoma cells treated with resveratrol were significantly increased after downregulation of miR-506. Conclusion Resveratrol inhibits proliferation, migration and invasion of melanoma cells by up regulation of miR-506.