Chronic inflammation has been implicated in the etiology of hepatocellular carcinoma (HCC). The C-reactive protein (CRP) genetic polymorphisms affected serum CRP concentrations and elevation of CRP has been considered as the hallmark of acute and chronic inflammation. In this study, we investigated the association between CRP genetic polymorphisms and HBV-related HCC risk in a Chinese population. Two polymorphisms in the CRP gene (rs3093059 and rs2794521) were examined in 192 HBV-related HCC patients, 277 non-HCC patients with HBV infection, and 192 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method. DNA direct sequencing was performed to validate the results of genotyping. We found that there were significant differences in the genotype and allele frequencies of the CRP gene rs3093059 polymorphism between the HBV-related HCC patients and the non-HCC patients with HBV infection. The rs3093059 TC genotype was associated with a significant increased HCC risk as compared with the TT genotype (odds ratio (OR) = 1.98, 95 % confidence interval (CI) 1.32-2.95, P = 0.001). The rs3093059 C allele was correlated with a significant increased HCC risk as compared with the T allele (OR = 1.65, 95 % CI 1.16-2.30, P = 0.005). Furthermore, the rs3093059 TC combined with CC genotypes were found to correlate with a significant increased HCC risk compared with the TT genotype in dominant model (OR = 1.92, 95 % CI 1.29-2.82, P = 0.001). However, we did not find any significant effect of CRP rs2794521 polymorphism on HCC risk in this population. In haplotype analysis between HBV-related HCC patients and non-HCC patients with HBV infection, the TC haplotype was found correlated with a significant increased HCC risk (OR = 1.750, 95 % CI 1.234-2.480, P = 0.001). The results suggested that the CRP rs3093059 polymorphism may contribute to increased HCC risk in HBV-infected patients in the Chinese population. Further large and well-designed studies in diverse ethnic populations are needed to confirm our results.