Association of the IVS1 -27G/A polymorphism of Krüppel-like factor 6 (KLF6) with gastric cancer was examined in a Chinese population comprising 300 gastric cancer patients and 300 healthy controls. Single-nucleotide polymorphism analysis was performed by amplifying intron 1 of KLF6 and sequencing the products. The KLF6 genotype IVS1 -27AA was significantly less frequent in gastric cancer patients than in controls and significantly less frequent in patients with advanced (stage III/IV) gastric cancer than in those with early (stage I/II) cancer. Stratification by location, Lauren's classification and histological differentiation revealed no significant differences in genotype distribution. Thus, in this Chinese population the KLF6 IVS1 -27AA genotype was associated with a decreased risk of gastric cancer and with cancer stage. Further study is required to clarify the mechanisms involved and, potentially, to facilitate the design of effective clinical trials.