In order to assess associations between the genetic polymorphism of L-myc and glutathione S-transferase M1 (GST M1) and the risk of hepatocellular carcinoma (HCC), a total of 46 surgically treated HCC patients who were seropositive in hepatitis B surface antigen (HBsAg) and 88 HBs-Ag positive controls were recruited for this study. L-myc and GST M1 genetic polymorphism was examined using a polymerase chain reaction-based restriction fragment length polymorphism assay on DNA extracted from liver and peripheral blood samples. There was no significant difference in GST M1 genotypes between HCC patients and matched controls. A gene dosage trend of association with HCC risk was observed for L-myc genotype. The dose-response relationship remained statistically significant in the multiple logistic regression analysis.