<i>Dlx4os</i> knockdown redirected melanoma cells to a more differentiated and less malignant phenotype, confirmed by differential expression of phenotypic state markers (<i>Sox10, Mitf, Tgfβ, Sox6, Mlana</i>), reduced their invasive and migratory potential, and delayed tumour progression <i>in vivo</i>. Here, SOX6 is linked to melanoma.