Gene-knockout technology is increasingly used as a powerful tool for establishing animal models of hyperuricemia (HUA). HUA gene-knockout animal models are not only helpful in revealing the molecular mechanisms of uric acid metabolism but are also of great value for evaluating potential therapeutic strategies. In this paper, the application of gene-knockout technology in HUA animal models is discussed in detail by reviewing the domestic and foreign literature, focusing on the knockout of urate oxidase, glucose transporter 9, and ATP-binding cassette transporter G2. The review provides a reference and guidance for the further establishment of HUA animal models by gene knockout technology.