Background: Tristetraprolin (TTP) is RNA-binding protein encoded by Zfp36 gene which regulates the mRNA stability of several important cytokines. Due to its critical role in control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL23 by myeloid cells, such as macrophages or DCs. The expression of TTP was studied in keratinocytes and explored its role in the imiquimod-induced psoriasis model. Objective: To study the possible role of Tristetraprolin in the pathogenesis of psoriasis. Methods: The study included 32 patients who were randomly assigned to two groups, group 1 included 22 patients with psoriasis and group 2 included 10 apparently healthy individual as a control group. Skin specimens were obtained by punch biopsy (3mm) from the skin lesion of the patients and normal skin of controls. Skin tissue from each case was homogenized in phosphate buffer saline (pH 7.4). The crude homogenate was centrifuged, and the resultant supernatant was removed and used for the measurement of Tristetraprolin level by ELISA. Results: Regarding to Tristetraprolin (ng/m protein) level, there was a significant difference between cases and control group regarding skin tissue TTP level. TTP was significantly lower in psoriasis patient when compared to controls (P value < 0.001). As regard relation between the level of TTP and the disease severity represented as PASI score; there was significant difference in TTP level between different grades (P value 0.001) with the lowest level in cases with severe psoriasis. Conclusions: Tristetraprolin may play a role in pathogenesis of psoriasis and may provide important clues to assist in the development of new therapeutic strategies for psoriatic patients.