Tumor necrosis factor (TNF) is a cytokine involved in inflammation and TNF-α might be synthesized ectopically in malignant tumors. Interleukin-6 (IL-6) is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. The present study is to investigate the relationship between genetic polymorphisms of the TNF-α and IL-6 genes and susceptibility to lung cancers in the ethnic group Han of North China. The genotypes in the -238G locus of TNF-α gene and the -572C locus of the IL-6 gene were determined by PCR-RFLP method in 138 patients with lung cancers and 138 healthy individuals. Software PHASE 1.0 was used to analyze the experimental data. The non-conditional logistic regression model was used to analyze the statistical association of genotypes and susceptibility in two groups adjusted by multiple factors. We found that the TNF-α and IL-6 polymorphisms may be a critical risk for the genetic susceptibility to lung cancers in the ethnic group Han of North China. SNP polymorphisms at the -238G locus of TNF-α gene and the -572C locus of the IL-6 gene were detected by the RFLP-PCR method. We found that high rates of single-base G-to-A alteration at the -238G locus of both alleles and high rates of single-base C-to-G alteration at the -572C locus of both alleles correlated with occurring of lung cancers. It is possible that the SNP markers at the -238G locus of TNF-α gene and the -572C locus of the IL-6 gene serve as biological markers of lung cancers upon further study in the future.