The roots and rhizomes of Smilax riparia, called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we examined the efficacy of S. riparia in reducing serum uric acid levels in a potassium oxonate-induced hyperuricemia mouse model. We observed that the total saponins of S. riparia could down-regulate renal mURAT1, resulting in the enhancement of urate excretion in the kidney of hyperuricemic mice. These results suggest that S. riparia could be an active anti-gout herbal medicine, which would contribute to the enhancement of uric acid excretion in the kidney.