BACKGROUND: Psoriasis vulgaris is a chronic, relapsing, inflammatory disorder marked by an intensified immune response. The role of immunogenetics in psoriasis is still poorly understood; however, experts agree that its expression depends on proin¬flammatory cytokines. Forkhead box class O3A (FOXO3a), a transcription factor, plays a crucial role in intercellular regulation, oxidative stress, deoxyribonucleic acid (DNA) repair, and cell death. OBJECTIVE: The objective of this study was to investigate the role of FOXO3a genetic polymorphism as a risk factor for psoriasis vulgaris and assess its possible relationship with disease severity. METHODS: A comparative case-control study included 53 patients with psoriasis and 41 matched healthy controls. We measured serum FOXO3a levels and used the PCR-RFLEP technique to detect FOXO3a genetic polymorphism (rs13217795) in both groups. RESULTS: Our results revealed significantly higher serum FOXO3a levels in the psoriasis group compared to the control group (p≤0.001). Serum FOXO3a levels were significantly higher in patients with severe psoriasis than in those with mild-to-moderate disease. FOXO3a genotypes found homozygous mutant genotype (TT) was substantially more frequent in the psoriasis group than in the control group. Furthermore, the T allele was more frequent in the psoriasis group than in the control group. CONCLUSION: The study indicates that rs13217795 polymorphism of the FOXO3a gene is strongly associated with susceptibility to psoriasis. Also, the serum level of FOXO3a is significantly higher in patients with severe psoriasis, compared to patients with mild-to-moderate psoriasis. This finding could be an area of future targeted therapy.