Psoriasis is a common chronic inflammatory hypertrophic skin disease characterized by abnormal proliferation and differentiation of keratinocyte and immune T cell. The pathogenesis of psoriasis has not been fully elucidated and there is no effective therapy in clinic. As a traditional Chinese medicine formula, Yangxue Jiedu Soup (YJS) has been used to treat inflammatory diseases caused by Yin Deficiency and Blood Dryness. The purpose of present study was to investigate the therapeutic effect and molecular mechanism of YJS on psoriasis model mice. Results showed that YJS effectively inhibited the hypertrophy, erythema and scales of psoriasis-like lesions to alleviate the pathological changes of skin lesions, and further decreased the production of TNF-α, IL-6, IL-1β, IFN-γ, IL-17 and IL-23. Meanwhile, YJS also significantly reduced keratinocyte proliferation and maintained immune system balance by inhibiting the expression of PCNA, Ki-67, CD4 + and CD8 + in psoriasis mice. Moreover, the results further indicated that YJS could inhibit TLR4 activation and NF-κB p65 nuclear transfer by suppressing HSP70 secretion to attenuate the inflammatory response in IMQ-induced mice, which provided a theoretical basis for the clinical use of YJS in the treatment of psoriasis.