Chronic inflammation has been implicated in the pathogenesis of colorectal cancer. The objective of this study was to evaluate the association of prediagnostic circulating levels of C-reactive protein (CRP), a biomarker of systemic inflammation, with subsequent development of colorectal cancer. Prediagnostic plasma CRP levels were examined among 288 colorectal cancer cases and 576 individually-matched controls nested within the Shanghai Men's Health Study (2002-06), a population-based cohort study of 61 482 Chinese men. The association between CRP levels and colorectal cancer risk was investigated. Baseline plasma CRP levels were 53% higher among men who subsequently developed colorectal cancer than among those who remained free of the disease (1.15 versus 0.75 μg/ml; P < 0.001). Multivariate analyses showed a dose-dependent relationship between CRP and colorectal cancer risk (P trend = 0.003); men in the highest tertile (CRP > 1.19 μg/ml) had 1.88-fold (95% confidence interval (CI): 1.24-2.86) increased odds of developing colorectal cancer compared with men in the lowest tertile (CRP < 0.45 μg/ml). The association was only significant for colon cancer, when cancer site was considered, and was predominantly seen for cases diagnosed within 4 years of blood collection; adjusted odds ratios for the highest versus the lowest tertiles were 3.28 (95% CI: 1.28-8.37), 3.68 (95% CI: 1.62-8.38) and 1.05 (95% CI: 0.56-1.97), respectively, for cases diagnosed <2, 2-4 and >4 years after blood collection. The findings from our study suggest that circulating CRP level is positively associated with colorectal cancer risk in Chinese men, and this association, at least in part, is explained by inflammation-related cancerous or precancerous processes.