ECRG1 (esophageal cancer related gene 1) is a novel candidate member of the tumor suppressor gene familypreviously found to be down regulated in human esophageal cancer (ESCC). So far no evidence regarding therole of the ECRG1 gene in this cancer has been reported from the Kashmir valley, located on the border of thehigh risk ‘esophageal cancer belt’. A case control study was therefore carried out with genomic DNA from 165newly diagnosed ESCC patients (cases) and 200 control subjects. DNA was analyzed for ECRG1 polymorphismsby RFLP PCR, gel electrophoresis and direct sequencing. A statistically significantly increased risk of ESCCwas found to be associated with the ECRG1 Arg/Gln and Gln/Gln genotype occurrence compared to the Arg/Arg genotype (odds ratio (OR) 1.698, 95% confidence interval (CI) 1.112–2.593); P= 0.0138) was observed.Statistically significant results were also obtained between the ECRG1 polymorphism and histophathologicalgrade, smoking, dysphagia, low fruit/vegetable intake and salt tea consumption.