Background: Esophageal squamous cell carcinoma (ESCC) incidence is high in Kazak Autonomous Prefecture, Xinjiang, China. Roasting food has been reported to be related with the risk of various cancers and is very popular in the area, and may be related with the risk of ESCC. The promoter methylation inactivation of p16 gene can increase the risk of ESCC. Thus, we want to know whether long-term roasting food is related with the risk of ESCC by effecting the promoter methylation of p16 gene. Materials and Methods: Ninety ESCC patients and 60 healthy subjects were recruited from Kazak Autonomous Prefecture. MassARRAY was used to detect p16 promoter methylation in ESCC tissues, as well as in normal esophageal tissues. The association between the p16 promoter methylation and daily roasting meat intake was examined. Results: Daily roasting meat intake was related with the risk of ESCC (p<0.01) and the mean CpG methylation rates of p16 promoter (p<0.01). In ESCC patients, the mean methylation rates of CpG 11-12 and CpG 33-34-35 were 29.4% and 37.4%, respectively, which was significantly higher than the rates in normal esophageal tissues (16.7% and 12.4%, respectively; p<0.01). The methylation of p16 promoter is also related with daily roasting meat intake (p<0.01) in Kazakh Chinese with ESCC. For the CpG methylation of the p16 promoter in the well, moderately and poorly differentiated ESCC, there are significant differences (p<0.05) for the 19 CpG units in the ESCC and controls. Conclusion: Roasting meat intake was associated with the risk of ESCC via effects on the methylation of p16 promoter. These results suggest roasting food intake should be limited in the diet.