Abstract: Objective: In order to explore the uric acid-lowering activity and mechanism of four traditional Chinese medicines, celery seed, dandelion, chicory and corn silk, and analysis of the main functional components with uric acid-lowering effect in these four kinds of traditional Chinese medicine compound extracts. Methods: Hyperuricemia model in zebrafish was induced by potassium oxazinate and sodium xanthine, then they were randomly divided into control group, model group, allopurinol group (136 µg/mL) and compound extract low, medium, high doses group (250, 500 and 1000 µg/mL), with 30 rats in each group. After continuous intervention for 24 h, the fluorescence level of uric acid and the gene expression levels of hypoxanthine phosphoribosyltransferase1 (HPRT1), glucose transporter9 (GLUT9), and organic anion transporter (OAT1) in zebrafish were measured. Using liquid chromatography-series high resolution mass spectrometer as the main method, and acetonitrile formate water as the mobile phase, gradient elution, ESI ion source positive and negative ion scanning mode, and then combined with software database search and related literature for component identification. Results: Compared with the model group, the low, medium and high dose groups of the compound extract could reduce the blood uric acid level of the hyperuric acid zebrafish model (P<0.01), and could effectively up-regulate the relative expression of HPRT1 and OAT1 and down-regulate the relative expression of GLUT9 in the hyperuric acid zebrafish (P<0.05). At the same time, 22 active ingredients including flavonoids and their glycosides, organic acids, coumarins, and terpenes were initially screened and identified, all of which are effective substances in the compound extract with a uric acid-lowering mechanism. Conclusion: The compound extract may play a multifaceted role in lowering uric acid by up-regulating the gene expression of HPRT1, OAT1, and down-regulating the gene expression of GLUT9 in the model group of zebrafish. The chemical components screened and identified can provide a reference for the next step of screening the target.