Background: Food insecurity is related to risk of adverse health outcomes such as obesity, but the explanatory factors underlying this association are still unclear. This study aimed to assess the association between food insecurity and obesity, and to explore potential mediation by sociodemographic and lifestyle factors. Methods: This cross-sectional study was conducted among 250 participants in a deprived urban area in the Netherlands. Data on sociodemographic and lifestyle factors, food insecurity status and diet quality were collected using questionnaires. Diet quality was determined based on current national dietary guidelines. BMI was calculated from self-reported height and weight. Regression analyses were performed to explore the association between food insecurity and BMI status. Mediation analyses were performed to estimate the total-, direct-, and indirect effect and proportion of total effect mediated of the food insecurity-obesity association. Results: The overall prevalence of food insecurity was 26%. Food insecurity was associated with obesity (OR = 2.49, 95%CI = 1.16, 5.33), but not with overweight (OR = 1.15, 95%CI = 0.54, 2.45) in the unadjusted model. The food insecurity-obesity association was partially mediated by living situation (proportion mediated: 15.4%), diet quality (- 18.6%), and smoking status (- 15.8%) after adjustment for other covariates. Conclusions: The findings of this study suggest an association between food insecurity and obesity. Living situation, diet quality and smoking status explained part, but not all, of the total association between food insecurity and obesity. Future longitudinal studies are warranted to examine the temporal order of the food insecurity-obesity association and potential mediators in this relationship. In addition, food insecurity and its potential consequences need to be taken into account in obesity prevention programs and policies.