Genetic variation of interleukin-28B (IL-28B) rs12979860 T/C polymorphism is associated with the immune response to interferon (IFN) therapy, which is applied in the treatment of chronic viral hepatitis induced by hepatitis B virus (HBV) and hepatitis C virus (HCV). These chronic liver diseases could progress to end-stage liver diseases, such as hepatocellular carcinoma (HCC). The aim of this study was to clarify whether there exists a causal association between IL-28B rs12979860 T/C polymorphism and development of HCC. In a meta-analysis of six studies with 850 cases and 811 controls, we summarized the data on the association between IL-28B rs12979860 T/C polymorphism and HCC risk and calculated ORs and 95 % CIs to estimate the association strength. We observed that IL-28B rs12979860 T/C polymorphism was positively associated with overall HCC risk (TT vs. CC: OR = 2.38; 95 %, 1.60-3.55; TT vs CT + CC: OR = 1.79; 95 %, 1.23-2.60). In the stratified analysis by ethnicity, the robust association retained in Caucasians with higher risk among TT carriers relative to the CC carriers. A similar trend was found in the studies of healthy controls when data were stratified by source of controls. The combined data suggest that IL-28B rs12979860 T/C polymorphism seems to augment the risk of developing HCC, especially in Caucasians.