We then used the phage display peptide library to screen a high affinity and specificity peptide (CY12-RP2) targeting PDPN, and found that CY12-RP2 could not only inhibit the proliferation, migration, and invasion of melanoma both in vitro and in vivo, but also could suppress the melanoma growth via modulating the proportion of subpopulation of immune cells, including T cells, macrophages, and NK cells. This evidence concerns the gene PDPN and melanoma.