Abstract: Objective: Explore and establish the best process of Taxilli Herba tea fermented by Aspergillus cristatus, and dig the potential mechanism of Taxilli Herba tea fermented by A. cristatus on the prevention and treatment effect of non-alcoholic fatty liver disease (NAFLD). Methods: In order to optimize the process of Taxilli Herba tea fermented by A. cristatus, analytic hierarchy process (AHP) was applied, main chemical components and organoleptic evaluation were taken as evaluation indexes, single factor experiments were taken, and orthogonal experiment was used. Moreover, to dig and evaluate the prevention and treatment effect of NAFLD, the model in Zebrafish larval induced by 0.1% egg yolk powder and 5 mmol·mL⁻¹ thioacetamide was used. Finally, technologies of UPLC-Q-TOF-MS/MS and network pharmacology were applied to select key compounds and core targets, and accomplish molecular docking. Results: The optimal fermentation process was as follows: The content of water was 35%, the time of pile-fermentation was 3 h, the concentration of A. cristatus was 1×10⁶ CFU·mL⁻¹, and fermentation time was 7 d. Taxilli Herba tea fermented by A. cristatus showed significant prevention and treatment effects in NAFLD (P<0.05) by lowering the level of total cholesterol, triglyceride, LDL cholesterol, aspartate aminotransferase and alanine aminotransferase. A total of fourteen differential metabolites was obtained by UPLC-Q-TOF-MS/MS analysis. The network pharmacology prediction result was reliable in a certain degree, while the key compounds such as echinulin and neoechinulin A showed good docking abilities with targets including NR1H4, LDLR, JUN, EGFR, STAT3 and so on. Conclusion: Taxilli Herba tea fermented by A. cristatus had obvious preventive and therapeutic effect in NAFLD, which could provide a theoretical foundation for further research and product development.