C-reactive protein (CRP) is one of the acute-phase proteins produced predominantly by hepatocytes in response to inflammation, and it has been widely reported that CRP genetic polymorphism is a risk factor for cardiovascular disease and ischemic stroke. In addition, we previously showed that the CRP 1846T/T genotype is related to lymph node metastasis in patients with esophageal cancer. In the present study, we investigated the correlation between CRP 1846C>T polymorphism and the clinicopathological characteristics of non-small cell lung cancer (NSCLC). The study participants were 146 Japanese patients who underwent curative surgery for NSCLC. DNA was extracted from tumor samples, and CRP1846C>T polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then correlated genotype with known clinicopathological factors. Five-year overall survival among patients with the CRP 1846T/T genotype was significantly lower than among those with the 1846C/C or C/T genotype (p = 0.002, p = 0.001; log-rank test). Multivariate Cox proportional hazard analysis revealed age, sex, pathological stage III, and 1846T/T (hazard ratio, 1.76; 95% confidence interval, 1.003-3.16; p = 0.049) to be independent factors affecting 5-year overall survival. These findings suggest the CRP 1846T/T genotype is an independent predictor of a poor prognosis in patients with NSCLC.