Abstract: Aim: To explore the potential active components, core targets and mechanism of Poria cocos in the treatment of metabolism-related fatty liver disease with anxiety and depression, and to provide theoretical basis for its clinical application. Methods: The active components and corresponding targets of Poria cocos were screened and obtained by network pharmacology method through TCMSP database and SwissTargetPrediction database. GeneCards database was used to obtain the related targets of metabolism-related fatty liver disease and anxiety and depression, and the intersection was used to obtain the potential targets of Poria cocos in the treatment of metabolism-related fatty liver disease with anxiety and depression. The protein-protein interaction network was constructed with the help of STRING database, and the core targets were screened after analysis by CytoScape software. GO function enrichment analysis and KEGG pathway enrichment analysis were performed through the DAVID database to explore its possible mechanism of action. Results: A total of 15 active components of Poria cocos were screened out, corresponding to 328 targets ; there were 74 intersection targets of metabolism-related fatty liver disease and anxiety and depression. The core targets are TNF, AKT1, IL6, PPARG, etc. GO enrichment analysis showed that biological processes mainly involved intracellular receptor signaling pathways, transcriptional regulation, etc. Cell components are mainly enriched in chromatin, endoplasmic reticulum, etc. ; molecular functions mainly include nuclear receptor activity, DNA binding, etc. KEGG enrichment analysis mainly involved non-alcoholic fatty liver pathway, insulin resistance, serotonin synapses and other signaling pathways. Conclusion: Poria may play a role in the treatment of metabolism-related fatty liver disease with anxiety and depression through multi-component, multi-target and multi-pathway synergistic effects on inflammatory response, metabolic regulation, neurotransmitter regulation and other processes.