Objective The association between ecological/lifestyle factors and major depressive disorder (MDD) have been provided but was in-consistent as characteristics of population including race, gender, etc. Methods Data were extracted from the Korean National Health and Nutrition Examination Survey and consisted of 35,839 adults in-cluding 1,537 with MDD. Ecological factors included age, sex, married status, education, family income, residence, occupation, BMI, self-recognition stress, and history of non-communicable disease. Smoking, drinking, regular exercise, total energy intake, and sleep was consisted for lifestyle factors. The relationship between MDD and ecological/lifestyle factors, was evaluated using the multiple logistic regression model after adjustment for covariates. Results The increased prevalence of MDD in men was related aged, unmarried, low educated, unoccupied, high BMI, and high self-recognition stress. To women, MDD prevalence was increased as aged, low educated and family income, resided in urban, unoccupied, high self-recognition stress and history of non-communicable disease. Current smoking/drinking and lack of sleep was positively related with prevalence of MDD in women. The relationship between lifestyle factors and MDD prevalence was influenced by ecological status, predominantly in women. Conclusion The relationship of lifestyle factors with MDD prevalence were observed and could be attenuated by various ecological factors, in women. Psychiatry Investig 2021;18(4):340-347