Background:　Psoriasis　is　a　common　chronic　inflammatory　skin　disease　characterized　by　epidermal　hyperplasia,　inflammatory　cell　infiltration　and　excessive　neovascularization.　It　was　previously　found　that　C10orf99　regulates　keratinocyte　proliferation　and　inflammation　in　psoriasis.　However,　the　role　of　C10orf99　on　angiogenesis　associated　with　psoriasis　is　unknown.　Methods:　We　used　imiquimod　(IMQ)-induced　psoriasis　mice　and　M5-induced　cellular　model　of　psoriasis　to　research　the　effects　of　C10orf99　knockdown　on　angiogenesis　in　psoriasis　in　vivo　and　in　vitro.　Results:　In　this　study,　our　data　showed　that　C10orf99　knockdown　ameliorated　imiquimod　(IMQ)-induced　red　plaques　in　mice　and　reduced　the　number　of　microvessels.　Furthermore,　we　found　such　an　effect　was　achieved　by　down-regulating　the　expression　of　vascular　endothelial　growth　factor　(VEGF)　and　metallomatrix　proteinase　2　(MMP2).　Consistently,　C10orf99　knockdown　significantly　downgraded　the　expression　of　MMP2　and　VEGF　in　cellular　model　of　psoriasis.　Conclusion:　These　results　suggested　that　C10orf99　could　regulate　angiogenesis　in　psoriasis　and　it　might　be　a　promising　potential　target　of　psoriasis.　©　2024　The　Author(s).　Skin　Research　and　Technology　published　by　John　Wiley　&　Sons　Ltd.