Psoriasis is an immune-mediated inflammatory keratotic skin disorder. Although some endogenous stimuli have been clarified to involve into the pathophysiology of psoriatic, the targeted drugs for treating psoriasis are still limited. Tripterygium wilfordii polycoride (TWP) extracted from Tripterygium wilfordii has potent anti-inflammatory and immune suppression functions, which has been widely used to treat autoimmune and inflammation-related diseases. In this paper, two injury models in vitro including Neutrophil elastase (NE) and NE plus Tumor necrosis factor-alpha (TNF-alpha) treated Hacat cells were established to investigate the therapeutic effect of TWP on psoriasis. Hacat cells viabilities were detected by CCK-8 kits. In addition, the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), NE and trappin-2 in the supernatant were assayed using ELISA kits; and the expression of intercellular adhesion molecule-1 (ICAM-1) was detected by western blotting. The results showed that the cell viabilities, NE and trappin-2 levels in Hacat cells were markedly increased after pretreatment with NE compared with the control group. However, TWP and trappin-2 could significantly down-regulated cell viabilities, NE and the NE/trappin-2 ratio. Furthermore, TNF-a and NE plus TNF-a could up-regulated the levels of IL-6 and IL-8 and the ICAM-1 protein expression, which were reversed by pretreatment with TWP or trappin-2. Thus, we concluded that TWP has inhibitory effects on proliferation and inflammatory cytokines secretion of Hacat cells by decreasing the ratio of NE and Trappin-2 level. These findings provide a new insight that will aid in elucidating the actions of TWP against psoriasis.