Objectives: Due to the currently inefficient therapies and the low 5-year survival rates of RCC patients, novel diagnostic, prognostic, and therapeutic markers are needed for this disease. Method: The cancer tissues and paracancer normal tissues were preserved in liquid nitrogen. In this report we analyzed the renal cell carcinoma tissues and paracancer normal tissues by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The 16 differentially expressed protein spots (p<0.05 by Student t-test) were identified by MALDI-TOF-MS and MS/MS. Results: 6 proteins were downregulated and 10 proteins were upregulated in clear cell RCC. The downregulated proteins were calbindin, ester hydrolase cllorf54, alcohol dehydrogenase, ammecr1-like protein, ADP/ATP translocase 3 and LYR motif-containing protein 5. The upregulated proteins were HIG1 domain family member 1A, Glutathione S-transferase P, Thioredoxin-dependent peroxide reductase, peroxiredoxin-6, CD2-associated protein, Annexin A5, gamma-enolase, retinal dehydrogenase 1, vimentin, and protein-glutamine gamma-glutamyltransferase 2. Conclusion: In brief, our data provide potential tumor markers for diagnosis of RCC.