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Objective: To observe the effect of Qishen decoction on dedifferentiation and autophagy of liver sinusoid endothelial cells (LSEC); Methods: LSEC were randomly divided into the control group, model group, Qishen Decoction low, medium, high dose group, and inhibitor group. The model was induced by 100μg/ml oxidized low-density lipoprotein (oxLDL) for 24 hours, and the corresponding drugs or medicated serum were given for intervention. The expression levels of VEGFR2 and ET1 were detected by RT-qPCR and immunofluorescence staining, the ultrastructure of LSEC was detected by transmission electron microscopy, the content of NO was detected by ELISA, the expression levels of autophagy related proteins (LC3BI, LC3BⅡ and p62) and endothelial function related proteins (eNOS and p- eNOS) were detected by west blot; Results: The results of transmission electron microscopy showed that Qishen decoction medicated serum could increase the number of fenestra and autophagy in LSEC cells, and inhibit the formation of basement membrane under endothelium. Compared with the model group, Qishen decoction medicated serum could significantly up-regulate the expression level of VEGFR2 mRNA and protein in LSEC, down regulate the expression level of ET1 mRNA and protein, the difference was statistically significant (P<0.05). In addition, Qishen decoction medicated serum could significantly increase the expression of LC3BII, p- eNOS, eNOS protein and the ratio of LC3BII/LC3BI, p- eNOS/eNOS, and reduce the expression of LC3BI and p62 protein in LSEC, which is statistically significant compared with the model group (P<0.05). Conclusion: Qishen decoction can inhibit the dedifferentiation of LSEC by promoting the autophagy level of LSEC, and then play an anti-fibrosis role.