Objective To study the expressions of keratin 10, 14 and 17 (KI0, K14, K17) in psoriatic lesions before and after the treatment with acitretin. Methods Thirty patients with moderate or severe plaque psoriasis were included in this study. The cohort consisted of 19 males and 11 females with an average age of 33.9 years, and disease course of 4 months to 30 years. Patients were treated with acitretin for 8 weeks which started with an initial dose of 20 mg per day for 1 week, then switched to 0.5-0.75 mg per kilogramme of body weight per day until symptom improvement, finally maintained at a dose of 10-30 mg per day. The expression of K10, K14 and K17 was detected by immunohistochemical technique before and after treatment with acitretin. The relationship between the disease severity and levels of keratins was evaluated. Results Prior to the treatment, increased expression of K14 and K17 was observed in lesions of patients along with the decreased expression of K10 compared with the normal controls. After treatment, the expression of K14 and KI7 significantly decreased (both P < 0.01), while that of K10 increased (P < 0.01), and there was still a statistical difference between the patients and normal controls (P < 0.01). A significant decrease was observed in the PASI score of patients (P < 0.01). The changes in the expression levels of K10, K14 and KI7 before and after treatment were somewhat correlated with the clinical course and severity of psoriasis. Conclusions Systemic aeitretin can affect the expression of K10, K14 and K17 in psoriatic lesions, but the extent of changes in their expression is not always consistent with the improvement of clinical manifestations.