Although Iran is a high-risk country for esophageal squamous cell carcinoma (ESCC), the contribution of overall nutrient intakes to this high incidence rate is not yet clear. The aim of this study was to examine the association between nutrient patterns and risk of ESCC in Iran. Forty-seven patients with ESCC and 96 frequency-matched hospital controls underwent private interviews, and dietary habits were collected using a validated food-frequency questionnaire. Factor analysis was conducted and two major nutrient patterns were retained; factor 1 (high in pantothenic acid, vitamin C, potassium, vitamin B6, magnesium, folate, thiamin, copper, carbohydrate, vitamin K, niacin, a-tocopherol, zinc, total fiber, fluoride, and polyunsaturated fatty acids) and factor 2 (high in saturated fatty acid, biotin, selenium, monounsaturated fatty acids, riboflavin, sodium, fat, cholesterol, calcium, phosphorus, protein, iron, vitamin E, manganese, vitamin D, and vitamin B12). Factor 2 was inversely associated with ESCC (OR = 0.06, 95% CI: 0.010.28; P = 0.008), whereas no significant association was found for factor 1 (OR = 0.45, 95% CI: 0.111.82). The results of the present study suggested a possible role for a nutrient pattern similar to factor 2 in reducing the risk of ESCC.