Hyperuricemia could lead to serious renal disease. It will advance our understanding of the mechanism of this disease to study the differentially expressed protein in renal tubular epithelial cells stimulated by elevated uric acid. We used SILAC coupled to LC-MS to study differentially expressed protein profile and to analysis the functional status of renal tubular epithelial cells stimulated by 600μM uric acid, and to investigate the potential biology function. The MS results were analyzed by online platform and further confirmed by western blotting. 789 differentially expressed proteins were identified, of which 42 proteins and 49 proteins were related with cell proliferation and cell apoptosis, respectively. Pathway analysis showed that MAPK signaling pathway was a key pathway related to the function of these proteins. In addition, prohibitin-2 was identified to be related to renal cell transdifferentiation stimulated by elevated uric acid. This work provides an overview of protein expression changes in HK-2 cells treated with elevated uric acid and will contribute to further study of cell apoptosis and fibrosis in renal disease patients. Copyright © 2011 S. Karger AG, Basel.