Background: Esophageal cancer is of major concern worldwide, ranking sixth as the most common cause of cancer mortality. Lifestyles such as cigarette smoking, alcohol consumption, and poor dietary habits have been suggested to be associated with the carcinogenesis of esophageal cancer. Objectives: This study aimed to determine the factors affecting and associated with esophageal cancer in Khorramabad city from 2012 to 2014. Patients and Methods: This is an analytical study of 48 patients with esophageal cancer, including 80 controls. The patients were selected on the basis of a census. The data were collected using a questionnaire, and Chi-square, t-test, and one way ANOVA analyses were performed using SPSS 19. Results: In this study, 57.8% males and 42.2% females participated, while the mean age of the patients was 68.46 years old, and the mean age of the healthy individuals was 59.79 years old. The findings of this study showed a family history of cancer, anemia, and smoking, and associations with education, occupation, socioeconomic status, blood group, consumption of hot drinks, as well as a history of gastroesophageal reflux. In addition, there was a significant relationship, but no significant association, between alcohol consumption and esophageal cancer. Conclusions: According to the results of this study, the necessary measures to modify the risk factors, such as educational programs and changing food consumption patterns in the subjects, are effective, and can reduce the risk of esophageal cancer.