Knockdown of HMGB1 further enhanced the inhibitory effects of etanercept on LPS-treated HaCaT cell viability and inflammation, while overexpression of HMGB1 notably reversed the inhibitory effects of etanercept on LPS-induced HaCaT cell viability and inflammation.<h4>Conclusion</h4>Etanercept inhibited proliferation and inflammation and promoted cell cycle arrest and apoptosis in LPS-induced HaCaT cells, and etanercept ameliorated inflammation in a psoriasis-like mouse model. This evidence concerns the gene HMGB1 and psoriasis.