Background: In Punjab, esophageal carcinoma has been reported as leading cancer in rural population. Reason for this high incidence of esophageal carcinoma in this region is unknown. The life style of people in Punjab is different from those of other areas in India. Therefore, the risk factors contributing to esophageal carcinoma in Punjab may also be different than the other parts of India. There are no previous studies on risk factors for high incidence of esophageal carcinoma in this region. Use of pesticides is much higher in Punjab state. Also there is no evidence available for association of use of pesticides/fumigants in occurrence of esophageal carcinoma. Hence this study is planned to identify the risk factors, especially the role of chemical toxicity (Pesticides/fumigants/heavy metals) associated with development of esophageal carcinoma among inhibitants of Punjab. Methods: A case-control design will be used to identify potential risk factors associated with development of carcinoma esophagus in Punjab. Cases will be recruited from PGIMER, Chandigarh, Population based cancer registry Mansa, Sangrur, SAS Nagar and Punjab Cancer control cell. For each esophageal cancer case 2 controls will be selected after matching for gender, age and area of residence. A pre designed questionnaire, including demographic characteristics, family cancer history, personal medical history, height, weight, life-style (habits such as smoking, tobacco chewing, alcohol drinking, etc.), dietary habits, fumigants and pesticide usage and practices etc, will be used. Urine samples will be taken for the analysis of pesticide metabolites. Heavy metals analysis will be done in water samples. Oral health will be examined for mucosal changes as well as for oral hygiene. Discussion: This study will results in identification of risk factors for high occurrence of esophagus carcinoma in Punjab, so that measures for early detection, prevention and control of esophagus carcinoma could be initiated.