psoriasis is a chronic inflammatory skin disease. The accumulation of IL-17 cytokines in the lesions leads to epidermis proliferation. Traditional Chinese medicine has a significant effect on psoriasis treatment. Among them, Tuhuaiyin is a representative prescription, which has an outstanding curative effect in acute and remission stage.To reveal the target and molecular mechanism of Tuhuaiyin, systematic pharmacology platform and database screening were used to construct the Tuhuaiyin interaction network with compounds, targets and diseases. The intervention of Tuhuaiyin on keratinocyte proliferation and inflammation was verified in the model of psoriasis-like lesions induced by imiquimod. The effect on the number and function of IL-17-producing cells was detected, and the regulatory effect of Tuhuaiyin on gut microbial was explored.32 selected active molecules in Tuhuaiyin acted on psoriasis biological processes. Tuhuaiyin significantly alleviates erythema and scales in the psoriasis like mouse model induced by imiquimod. Excessive proliferation of keratinocytes and infiltration of inflammatory cells were restrained in the dermis by using Tuhuaiyin. The expression of IL-17 was down-regulated in skin and peripheral blood. The proportion of IL-17-producing cells was decreased in immune organs. And phosphorylation of JNK inhibited in skin lesions. At the same time, the change of gut microbial diversity in the psoriasis-like model was improved.our study predicted and verified the molecular immunological mechanism of Tuhuaiyin, alleviated the abnormal proliferation of keratinocytes by inhibiting the proportion of IL-17-producing cells and the expression of IL-17 cytokines. Taken together, our data identify the therapeutic potential of Tuhuaiyin for psoriasis.Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.