Psoriasis vulgaris is a systemic disorder with an underlying immune dysregulation that predisposes to inflammatory skin lesions. Meanwhile, tumor necrosis factor alpha-induced protein 3 (TNFAIP3) has been described as a protective molecule against the deleterious effects of uncontrolled inflammation. In this study, we compared the expression levels of TNFAIP3 in blood and psoriatic skin biopsies from psoriatic patients versus those in normal individuals. Additionally, the levels of TNFAIP3 protein in psoriatic skin biopsies were compared to those in normal individuals. Thirty psoriatic patients and 30 healthy participants (control group) were enrolled. The expression levels of TNFAIP3 in blood and skin were measured by quantitative reverse transcription PCR, while the skin levels of TNFAIP3 protein were measured by western blot. Psoriatic patients showed significantly lower expression levels of TNFAIP3 in psoriatic skin and blood (P< 0.001) as well as of TNFAIP3 protein in psoriatic skin (P< 0.001) compared to controls. A significant lower expression of TNFAIP3 and TNFAIP3 protein in psoriatic skin was detected in moderate/severe cases compared to mild cases (P = 0.004 and 0.003 respectively). Moreover, a significant negative correlation was found between TNFAIP3 mRNA in psoriatic tissue and psoriasis area severity index values (rs = -0.382, P-value = 0.037). In conclusion, TNFAIP3 may serve as a predictive and prognostic biomarker in psoriatic patients. Enhancing the expression and/or function of TNFAIP3 in the affected cell type may be a promising therapeutic strategy.