Polymorphisms of the H2A histone family member X (H2AFX) gene have been associated with decreased non-Hodgkin lymphoma (NHL, -417AA) risk and increased breast cancer (1654AG/GG, and -1420GA/AA) risk. We investigated whether H2AFX polymorphisms are associated with the risk of NHL and its subtypes in 573 NHL Korean patients and 721 cancer-free control subjects, using high resolution melting polymerase chain reaction and an automatic sequencer. There was no association between polymorphisms and the risk of overall NHL, all B cell lymphoma, or all T cell lymphoma. However, the -1420 AA genotype was associated with decreased diffuse large B cell lymphoma (DLBCL) risk (OR, 0.65; 95% CI, 0.43-0.97), and there was a trend for allele dose-effect (p-trend=0.03). The -1187 CC genotype was associated with decreased DLBCL risk with borderline significance (OR, 0.70; 95% CI, 0.48-1.02). There was a trend for an allele dose-effect with borderline significance (p-trend=0.06). These results suggest that the -1420 AA genotype of H2AFX may be associated with reduced DLBCL risks in the Korean population.