Anaphylatoxin C5a, a potent pro-inflammatory peptide produced in the process of complement activation, was proved to have a vital role in tumor initiation and progession by previous investigations. However whether it could act as a prognostic marker remains unknown. Here we retrospectively enrolled 272 ccRCC patients undergoing nephrectomy in Zhongshan Hospital, Shanghai between 2005 and 2007. C5a level was assessed by immunohistochemistry and its association with clinicopathologic features and prognosis were evaluated. Our results indicated that high tumoral C5a level was associated with poor overall survival (OS) (hazard ratio = 1.753, 95% CI 1.068-2.878, P = 0.026). In addition, tumoral C5a could significantly stratify patients' prognosis both in advanced stage (TNM III + IV) and intermediate/high risk group (SSIGN score ≥4) (P < 0.001 and = 0.008, respectively). Furthermore, incorporating tumoral C5a with other parameters could improve the predicting accuracy, compared with TNM and SSIGN system (c-index = 0.789, 0.713 and 0.727, respectively). In conclusion, tumoral C5a is an independent adverse prognostic biomarker for clinical outcome of ccRCC patients after nephectomy.