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Shantou, China, is one of the endemic regions of esophageal cancer (EC) in the coastal areas, but the relationship between the multiple exposures of total N-nitroso compounds (TNOCs) and the high risk of EC to date is unclear. This study is to estimate the potential integrative role of multiple exposures of environmental and endogenous TNOC on the EC risk. We collected randomly the samples of 72 h diet and 24 h urine from 256 healthy male (aged 30–65 years) in the high- and low-risk area for EC, and determined the contents of TNOC and 4 N-nitrosamino acids (NAAs) by a method of chemical fission-Thermal Energy Analyzer (TEA) and gas chromatography — TEA, respectively. We used TNOC and NAAs index to evaluate the integrative effect of multiple TNOC exposures on the EC risk by a logistic model. TNOC intake and urinary TNOC content were higher in the high-risk subjects than that in the low-risk subjects by 1.60 μmol/day and 1.45 μmol/L, respectively. TNOC intake, urinary TNOC content and its interaction were significant factors involved in the higher risk of EC (R 2 =0.685, p =0.000) with predicted Correct Class of 85.6%. The risk of the occurrence of a larger SMR of EC may increase by 4.841-fold for every 1 μmol/day increase in TNOC intake (95% CI 2.370–9.888, p =0.000) and by 4.113-fold for every 1 μmol/L increase in urinary TNOC content (95% CI 2.108–8.023, p =0.000), respectively. The integrally role of multiple exposures of TNOC in environment and in vivo may increase the risk of EC in the coastal areas in eastern Guangdong, China. [Copyright &y& Elsevier]