Hyperuricemia (HUA) caused by high serum uric acid (UA) level can lead to a range of metabolic diseases, such as gout, cardiovascular disease and diabetes. The reduction of crucial UA precursors of both inosine and guanosine is a potential method to control HUA. Here a promising bacterial strain for biodegrading both inosine and guanosine were successfully isolated from Baijiu cellar mud and identified as Lysinibacillus fusiformis-YC01 by ANI analysis. Initial 490 mg/L of inosine and 612 mg/L of guanosine were completely biodegraded by YC01 within 18 h at 38 °C. In addition, the initial 357 mg/L of inosine and 365 mg/L of guanosine were also removed by the cell-free extracts of YC01 at a protein concentration of 0.13 mg/mL within 16 h. Furthermore, the whole genome analysis of YC01 revealed that purine nucleoside phosphorylase and purine nucleosidase played key roles in the biodegradation of inosine and guanosine, which encoded by gene deoD and gene iunH. These findings indicated that YC01 could biodegrade inosine and guanosine, and provided the new valuable insights into microbial removal of UA precursors for the amelioration of HUA.