Abstract： Objective： To observe the curative effect of the therapy of Xiaoyao San Prescription combined with Silymarin Capsules on non-alcoholic fatty liver disease (NAFLD) with syndrome of liver depression and spleen deficiency. Methods：A total of 90 NAFLD patients with syndrome of liver depression and spleen deficiency were selected and divided into the control group and the treatment group according to random number table method， with 45 cases in each group. The two groups were given non-drug measures. The control group was given Silymarin Capsules orally，and the treatment group was additionally given Xiaoyao San Prescription based on the treatment of the control group. Both groups were treated for 12 weeks. The clinical effects in the two groups were compared. The changes of liver function indexes [aspartate aminotransferase (AST)， alanine aminotransferase (ALT)， γ -glutamyl transpeptidase (GGT)]， blood lipid indexes [total cholesterol (TC)， triglyceride (TG)， high-density lipoprotein (HDL-C)， lowdensity lipoprotein (LDL-C)] and relative protein levels of TLR4/NF- κB signaling pathway in serum [serum TOLL-like receptor 4 (TLR4)， myeloid differentiation factor 88 (MyD88)， nuclear transcription factor κB (NF-κB)]，interleukin-6 (IL-6)，tumor necrosis factor-α (TNF-α) were compared between the two groups before and after treatment. Results：After 12 weeks of treatment，the total effective rate was 91.11% in the treatment group and 73.33% in the control group ， the difference being significant (P ＜ 0.05). After 12 weeks of treatment， the levels of AST， ALT and GGT in the two groups were decreased when compared with those before treatment (P＜0.05)，and the above three levels in the treatment group were lower than those in the control group (P＜0.05). After 12 weeks of treatment， the levels of TC， TG and LDL-C in the two groups were decreased when compared with those before treatment (P＜0.05)，and the levels of HDL-C were increased when compared with those before treatment (P＜0.05)；the levels of TC， TG and LDL-C in the treatment group were lower than those in the control group (P＜0.05)， and the levels of HDL-C were higher than those in the control group (P＜0.05). After 12 weeks of treatment，serum levels of TLR4， MyD88， NF- κB， IL-6 and TNF- α in the two groups were decreased when compared with those before treatment (P＜0.05)， and the above five levels in the treatment group were lower than those in the control group (P＜0.05). Conclusion： The therapy of Xiaoyao San Prescription combined with Silymarin Capsules has a definite therapeutic effect on NAFLD with syndrome of liver depression and spleen deficiency. It can effectively improve liver function and blood lipid status， regulate serum TLR4-NF- κB signaling pathway and inhibit inflammation.