AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China.METHODS: A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus, hypertention, hepatolithiasis, primary sclerosing cholangitis, liver fluke infection (Clonorchis sinensis), was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression.RESULTS: Compared with controls, ICC patients had a higher prevalence of HBsAg seropositivity (48.4% vs 9.6%, P < 0.000), and hepatolithiasis (5.4% vs 1.1%, P = 0.001). By multivariate analysis, the significant risk factors for development of ICC were HBsAg seropositivity (adjusted OR, 8.876, 95% CI, 5.973-13.192), and hepatolithiasis (adjusted OR, 5.765, 95% CI, 1.972-16.851). The prevalence of anti-HCV seropositivity, diabetes mellitus, hypertention, cigarette smoking, and alcohol consumption were not significantly different between cases and controls.CONCLUSION: These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.