Background and aims: Increasing evidence suggests that elevated serum levels of C-reactive protein (CRP) are associated with poor survival in many malignant tumors. However, the prognostic value of CRP in advanced gastric cancer (AGC) remains uncertain. This study was undertaken to evaluate the significance of serum CRP as a biomarker of long-term survival in patients with AGC. Methods: The serum CRP levels of AGC patients were analyzed for clinicopathological significance. Data were collected retrospectively for 244 patients treated between October 1, 2006 and September 30, 2013. The prognostic effect of serum CRP levels was evaluated. Results: The baseline CRP level before chemotherapy was significantly associated with overall survival. The median survival was 351 days for patients with CRP >= 10 mg/L and 370 days for patients with CRP < 10 mg/L (p = 0.033). Cox analysis revealed CRP to be an independent prognostic factor for overall survival. In the 93 patients whose baseline CRP was >= 10 mg/L, a cutoff point of 22% for the CRP declining rate provided optimum sensitivity and specificity for 1-year survival based on ROC curves. A CRP declining rate > 22% was found to predict longer overall survival (410 days versus 299 days; p = 0.001). Conclusions: Elevated serum CRP baseline levels before chemotherapy were associated with reduced overall survival in patients with AGC. The CRP declining rate was also associated with overall survival. The CRP baseline concentration before chemotherapy and CRP declining rate after chemotherapy may be used as novel, widely available and real-time independent prognostic and predictive markers of AGC.