It has been found that severe lipid metabolism disorders are often present in patients with Psoriasis, including decreased levels of high-density lipoprotein (HDL). This study initially explored the impact of HDL level variations on psoriasis by collecting. This study collected 12 blood samples and 9 skin samples from psoriasis vulgaris and psoriasis vulgaris with reduced HDL levels and performed bulk RNA sequencing. The genes expressed explicitly in both tissue and blood samples from psoriasis vulgaris patients with low HDL levels were selected to explore their molecular regulation in psoriasis vulgaris further, to elucidate the pathogenesis of psoriasis. A total of 421 specific DEGs in blood and 143 specific DEGs in skin from PN groups were obtained, and these genes were enriched in the terms and pathways related to inflammation and immune system. Also, biomarkers were screened out with same expression pattern in both blood and skin samples. Five intersecting differential genes (METRNL, NDEL1, HLA-DRA, MZB1, MKRN3) were obtained. Their function was further predicted. In conclusion, our research identified five biomarkers in psoriasis that are associated with low HDL levels. Furthermore, our findings revealed that alterations in HDL levels in psoriasis may exacerbate the clinical manifestations of psoriasis through regulation of immune response and lipid metabolism.Copyright © 2024. Published by Elsevier B.V.