The association between hepatocellular carcinoma (HCC) and the 61A>G polymorphism in the epidermal growth factor (EGF) gene has been analyzed in several studies, but results have been inconsistent. The aim of this study was to integrate previous findings and explore whether this polymorphism is associated with susceptibility to HCC. A meta-analysis was performed by searching PubMed, Web of Science, and Cochrane Library databases. Data were extracted using predefined form and pooled odds ratios (OR) with 95% confidence intervals (CI) and were calculated to evaluate the strength of this association. Five studies involving 690 cases, 514 healthy controls, and 1419 controls with cancer-free liver diseases were identified. On the basis of healthy controls, the significant main effects on HCC risk were observed in a heterozygote comparison (OR=1.76, 95% CI 1.07-2.90, p=0.02) and a dominant genetic model (OR=1.65, 95% CI 1.03-2.66, p=0.04). On the basis of the controls with cancer-free liver diseases, a significantly increased risk of HCC was found in all the genetic models. Subgroup analyses stratified by ethnicity and etiology of HCC also showed positive associations. The EGF 61G allele is a risk factor for developing HCC without the influence of ethnic and etiological diversity.