The promoter methylation of the FHIT gene has been associated with susceptibility to different cancers, including a role in the early pathogenesis of lung cancer. We investigated the aberrant promoter methylation of FHIT in lung cancer in the Han population of southern-central China. Blood samples from 123 lung cancer patients of different clinical stage and histological grading and 105 healthy control samples were collected. Methylation-specific polymerase chain reaction (MSP ) was performed to analyze the methylation status of FHIT. Aberrant promoter methylation of the FHIT gene was 34.15% (42/123) in cancer patients, but in none of the 105 controls. Significant association was found between the lung cancer cases and controls (OR=2.296; 95% CI=1.95-2.705; p < 0.01). Furthermore, we found that aberrant promoter methylation of the FHIT gene showed a highly significant association with clinical stage I and not with clinical stage IV in lung cancer (p < 0.05). These findings suggest FHIT methylation is associated with a higher susceptibility and has a prognostic significance in early stage lung cancer in the Han population of southern-central China and may represent a marker for progressive disease.