Objective: To assess anti-psoriatic activity of the methanol extract and the isolated flavonoid quercetin from the rhizome of Smilax china (S. china) Linn. Methods: Mouse tail test was used for the evaluation of anti-psoriatic activity. Methanol extract (100 and 200 mg/kg b.w.) and isolated flavonoid quercetin (25 and 50 mg/kg b.w.) were tested in Swiss albino mice. Parameters studied in the mouse tail test were changes in epidermal thickness and percentage orthokeratotic values. The anti-inflammatory role of the methanol extract and isolated flavonoid quercetin was evaluated using carrageenan-induced pleurisy in rats. In vitro antiproliferant assay on HaCaT cell lines was also carried out. Results: The isolated flavonoid quercetin from the rhizome of S. china produced significant orthokeratosis (P<0.01) in the mouse tail test. In epidermal thickness, a significant reduction with respect to control was observed in groups treated with retinoic acid and isolated flavonoid quercetin. The methanol extract (200 mg/kg) and isolated flavonoid quercetin (50 mg/kg) showed anti-inflammatory effect in terms of significant inhibition (P<0.001) in leukocyte migration. Maximum antiproliferant activity was shown by isolated flavonoid quercetin (IC50, 62.42±10.20 μg/mL). Conclusions: From the above data, the flavonoid quercetin shows significant orthokeratosis, anti-inflammatory and maximum antiproliferant activities. To our knowledge, this is the first report on the anti-psoriatic effect of the flavonoid quercetin which is promising for further investigations to prove its anti-psoriatic activity.