Anoikis is a programmed cell death that occurs when cells detach from the extracellular matrix (ECM). Its role in psoriasis remains unclear. This study aims to explore the relationship between psoriasis and apoptosis, focusing on anoikis-related mechanisms. Differentially expressed genes (DEGs) in psoriasis were identified using the GEO database and overlapped with anoikis-related genes from GeneCards to find differentially expressed anoikis-related genes (DE-ARGs). A PPI network was constructed, revealing eight hub DE-ARGs. These were then analyzed using GO, KEGG and ssGSEA. Immune infiltration cells and molecules were examined, and single-cell data analysis, immunohistochemistry, qRT-PCR, Western blotting, gene mapping, and drug prediction were performed. Eighteen DE-ARGs were identified, with STAT3 and BIRC5 as key DEGs. Enrichment analysis showed DE-ARGs were related to the regulation of anoikis and positive regulation of epithelial cell proliferation. Notable differences in dendritic and mast cells were observed between psoriasis lesions and no-lesion samples. Elevated expression of BIRC5 and STAT3 in psoriasis lesions was confirmed through qRT-PCR, western blotting and immunohistochemistry. This study establishes a relationship between anoikis and psoriasis, where STAT3 and BIRC5 play important roles. STAT3 and BIRC5 may serve as potential targets for the prevention and treatment of psoriasis.