Background/Objectives Progranulin (PGRN) is a secreted glycoprotein that was investigated in many skin diseases. It plays an important role in inflammatory response and autophagy which could be mediated through Wnt/β‐catenin pathway. However, the role of PGRN in pathogenesis of psoriasis has not been clearly well‐known. Therefore, we aimed by this study to investigate the possible role of progranulin in psoriasis pathogenesis through evaluation of its immunohistochemical expression in lesional and perilesional skin of psoriasis patients and to investigate if its hypothesized role is mediated through β‐catenin or not. Methods This case‐control study was carried out on 37 patients presented with variable degrees of psoriasis vulgaris severity vs 37 age and sex‐matched apparently healthy volunteers. Psoriasis area and severity index (PASI) score was used to evaluate the severity of psoriasis. From all cases (lesional and perilesional) and controls, skin biopsies were taken for histopathological and immunohistochemical evaluation of PGRN and β‐catenin. Results There was a significant stepwise upregulation of PGRN from controls (76.2 ± 11.9) to perilesional (178.7 ± 11.8) and lesional (242.7 ± 12.7) psoriatic skin (P < 0.001). PGRN expression was significantly correlated with psoriasis severity (r = 0.61; P < 0.001). β‐catenin showed a significant stepwise downregulation from control (210.0 ± 19.3) to perilesional (131.4 ± 9.2) and lesional (97.3 ± 11.5) psoriatic skin(P < 0.001). There was a significant negative correlation between PGRN and β‐catenin expression in psoriatic skin (P < 0.001). Conclusions Progranulin has a pro‐inflammatory effect in the psoriasis pathogenesis, which could be mediated through a decreasing β‐catenin expression in psoriasis. PGRN may be used as a target for immunotherapy in psoriasis management program.