Objectives: To investigate the prognostic role of C-reactive protein in patients with advanced renal cell carcinoma treated with sunitinib. Methods: A total of 41 consecutive patients with advanced clear-cell renal cell carcinoma treated with sunitinib between December 2008 and August 2011 were included in this study. Logistic regression analysis estimated the relative importance of non-tumor variables, including C-reactive protein, and selected adverse events as predictive factors for sunitinib responses. Results: Overall, 11 patients (26.8%) showed a partial response and 10 patients (24.4%) had stable disease. On univariate analysis, Memorial Sloan-Kettering Cancer Center non-poor risk, normal C-reactive protein, handfoot skin reaction, altered taste, fatigue and leukopenia were significantly correlated with objective responses (P = 0.020, 0.001, 0.006, 0.006, 0.023 and 0.037, respectively). On multivariate analysis, normal C-reactive protein was independently associated with objective response (P = 0.016). Patients with a normal level of C-reactive protein (=0.30 mg/dL) had a significantly higher partial response plus stable disease rate (84.6% vs 35.7%, P = 0.002) and significantly longer progression-free survival (median 19.0 vs 6.0 months, P = 0.036) than patients with an elevated level of C-reactive protein. Conclusions: C-reactive protein is an independent prognostic indicator for patients with advanced renal cell carcinoma treated with sunitinib.