Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia. Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate. The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes, pathological changes, non-target metabonomics and network pharmacology. Results Baicalein could reduce the contents of serum uric acid, creatinine and blood urea nitrogen, reduce the inflammatory injury of renal tissue, up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein. Nine disease-related targets such as BCL2, SIRT1 and XDH were screened by network pharmacology. Six key metabolic pathways including nicotinic acid and nicotinamide metabolism, caffeine metabolism and purine metabolism were screened by metabonomics analysis. Conclusions Baicalein can treat hyperuricemia and reduce renal injury, and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.