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Abstract Evaluating the effects of nutrients in our diet need entering more than one nutrient item (or food groups) in a single statistical unit. With this method, not only we considered the effects of a nutrient in health-related subjects, but also we find out the consequences of replacing and deleting nutrients on our outcome. In nutritional epidemiology, substitution analysis is used to evaluate the effects of various nutrients on a specific outcome. In the substitutional analysis, when some nutrients or foods included in a single statistical model, then investigation of the effects of several nutrients on the specific outcome is more achievable. The objective of this paper is to provide a detailed examination of the key aspects of substitution analysis in nutritional sciences.Keywords: substitution analysis, dietary intake, nutritional epidemiology