Hyperuricemia (HUA) is a metabolic disease characterized by disorders of uric acid synthesis and excretion. Theabrownin (TB), a macromolecular water-soluble pigment from black tea, can bring beneficial effects on human health. The effects and underlying molecular mechanisms of TB on HUA animals and patients are still unclear. This study aimed to explore the potential function and the possible mechanisms of TB in improving HUA. Our results demonstrated that TB could reduce the levels of serum uric acid and improve renal pathological damage in HUA mice by inhibiting xanthine oxidase (XOD) activity in the liver and increasing the expression of uric acid transporter proteins in the kidney. Furthermore, TB was proven to suppress autophagy, inflammation, and fibrosis in the kidney of HUA mice. Moreover, a self-controlled clinical trial showed that TB drinking daily for 12 weeks could decrease serum uric acid levels in HUA patients without any adverse effects. In conclusion, TB exhibits significant potential in decreasing serum uric acid levels both in HUA mice and patients, offering a novel approach to HUA treatment.