BACKGROUND: In psoriasis, damage-associated molecular patterns (DAMPs) released by damaged local tissue act as danger signals and trigger inflammatory responses. Statins, in addition to cholesterol-lowering, have anti-inflammatory effects. We sought to assess the effectiveness of atorvastatin in attenuating plasma DAMPs and inflammatory cytokines in adults with psoriasis. METHODS: In this prospective 3-month study, we included 21 eligible psoriatic patients who received oral atorvastatin 10 mg/day and 14 non-psoriatic controls. Blood samples for DAMPs measurement were collected at baseline and 3 months. Additionally, efficacy outcomes were estimated using psoriasis severity index and dermatology-specific quality of life index scores at baseline and 3 months. RESULTS: Compared to control, psoriatic plasma showed a decrease in the decoy of DAMPs, the soluble (s) receptor for advanced glycation end products (sRAGE), and increases in the DAMPs S100B, S100A7, S1100A12, S100A8/A9, DJ-1, the inflammatory cytokines IL-6, IL-1β and TNF-α. Atorvastatin for 3 months improved efficacy scores, increased sRAGE, and decreased DAMPs and inflammatory cytokines toward control levels. Mechanistically, in the immortalized embryonic fibroblast Swiss mouse cell line NIH3T3s, S100A12, and S100A7 induced an inflammatory response and atorvastatin increased sRAGE in the medium. CONCLUSION: Statin therapy is effective in lowering DAMPs-induced inflammation in psoriasis patients. The main limitation of our study is the small sample size, and the findings should be confirmed in a larger cohort.