Raf kinase inhibitory protein (RKIP) gene is considered to be a suppressor of metastasis involved in various carcinomas. In the present study, we observed that promoter methylation repressed the expression of RKIP in TE-13 cell line. 5-Aza treatment and stable transfection of RKIP resulted in a significant inhibition of TE-13 cell proliferation. The promoter hypermethylation of RKIP was found to occur in dysplastic tissues and a close correlation was noted between RKIP methylation and the loss of mRNA and protein expression of the gene in ESCC specimens. In summary, RKIP may act as a tumor suppressor gene in esophageal cancer.