Gut-enriched Kruppel-like factor (GKLF) is a newly identified eukaryotic zinc finger protein expressed extensively in the gastrointestinal tract, the expression of which is associated with growth arrest. GKLF expression in the tumor was compared to normal mucosa in esophageal squamous cancer patients, using semi-quantitative RT-PCR. Expression of GKLF mRNA was detected all of 17 cases of esophageal squamous cancer. Decreased expression of GKLF mRNA was observed in 14 of esophageal squamous cancer patients compared to normal esophageal tissues adjacent to tumor from the same patient. Serum deprivation induced overexpression of GKLF was observed in the primary culture of human fibroblast and this induction was decreased in an esophageal squamous cancer cell line EC9706. Sequencing of GKLF cDNA from EC9706 showed no mutations in the coding region. The results demonstrate that GKLF expression in esophageal squamous cancer is down-regulated.