Background: Psoriasis is a common inflammatory skin disease with a global incidence of 1.9%. Its clinical features are red scaly plaques that can affect any part of the body. The aim of this study is to investigate K5 and K14 tissue levels and the possible role of microRNA 21 on their levels in keratinocytes of psoriasis vulgaris patients. Methods: The present study included 80 participants divided into 40 psoriasis vulgaris patients and 40 healthy subjects of matched age and gender. All participants were subjected to full history taking and clinical examination. Quantitative real-time PCR was done to estimate the expression level of tissue microRNA 21. As well as estimation of tissue levels of K5 and K14 by ELISA techniques. Results: Results revealed that both K14 level and microRNA 21 were significantly increased in Psoriasis patients compared to the healthy group with p-value Conclusions: Marked elevation of K14 was found in psoriasis vulgaris epidermis, though K5/K14 is usually paired there was a discrepancy between their levels in the psoriatic lesions, also miRNA-21 was markedly upregulated and was negatively correlated to the high levels of K14. Further studies are needed on wider population for more elucidation of their relationship and their role in the pathogenesis of Psoriasis vulgaris.