Objective: It has been reported by some prospective studies that C-reactive protein (CRP) is associated with cancer risk. However, the correlation between CRP and digestive system cancers has not been evaluated in Chinese females. We conducted a large population-based cohort study to investigate whether elevated level of CRP in serum is associated with an increased risk of digestive system cancers in Chinese women. Methods: From the Chinese Kailuan Female Cohort, 19, 437 women were enrolled in this study in July 2006, and all of the subjects were followed up through 2014. At the baseline investigation, the serum levels of high-sensitivity CRP (hsCRP) were tested for all subjects, and demographic information and risk factor data were collected. Multivariable Cox proportional hazards regression model was used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI) for the baseline levels of hsCRP after adjusting for age, marital status, smoking, drinking, body mass index (BMI), diabetes and physical activity, and risk of digestive system tumors (including colorectal cancer, stomach cancer, pancreas cancer, liver and gallbladder cancer, and other cancers). Results: By Dec 31, 2014, a total of 100 incident cancer cases were observed, including 47 colorectal cancers, 17 stomach cancers, and altogether 29 pancreas, liver and gallbladder cancers. All the subjects investigated were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The 8-year cumulative incidence of digestive system cancers were 405/100 000, 520/100 000 and 787/100 000 in these 3 groups, respectively (Log rank test χ2 = 8.37, P=0.015). Compared to those with lower hsCRP levels (<1 mg/L), the women with higher hsCRP (>3 mg/L) had a significantly increased risk of pancreas, liver and gallbladder cancers (HR = 2.70, 95% CI = 1.06-6.91; Ptrend = 0.036). Conclusions: Elevated levels of hsCRP at baseline may be associated with increased risk of certain digestive system cancers.