Background As indicators of the systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been proposed to predict the clinical outcome in some cancers. The purpose of this study was to investigate the impact of NLR and PLR on the prognosis of gastric cancer. Methods From 2000 to 2009, 1986 consecutive patients who underwent curative surgery for gastric cancer were enrolled. The optimal cutoff value of PLR and NLR was determined according to receiver operating characteristic analysis. We categorized the patients into the high or low PLR and NLR group based on the cutoff value, and the clinical features of these two groups were comparatively analyzed. Results The high NLR and PLR groups were significantly associated with poor prognosis. The NLR was an independent prognostic factor for overall survival hazard ratio (HR) = 1.403; p  = 0.023; however, the PLR was not ( p  = 0.788). Conclusions Although both the PLR and NLR can reflect the prognosis, the NLR is more predictive of overall survival than the PLR.