Objective: Variations in the tumor necrosis factor-alpha (TNF-α) gene may lead to changes in the level of TNF-α associated with the susceptibility to cancer. This study is designed to determine the association of TNF-α promoter polymorphisms with the susceptibility of cervical cancer among women living in Southwest China. Methods: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, we analyzed the genotype and allele distributions of 4 single-nucleotide polymorphisms (SNP) of TNF-α gene in 239 cervical cancer patients and 110 controls. Results: Compared to controls, cervical cancer patients show a significant increase in the frequency of GA genotype at -308 G/A, and a significantly decreased frequency of the CT genotype. A significant decrease in the frequency of the T allele at -857 C/T (P<0.05) was also found. No significant differences of SNP genotype and allele at TNF-α-863 C/A and -238 G/A were observed between the 2 groups. Conclusion: An SNP at TNF-α -857 C/T and -308 G/A, but not -863 C/A or -238 G/A, were significantly associated with an increased risk of cervical cancer in the studied population. © 2011 by The American Society for Clinical Pathology.