Background: Household-food-insecurity, is situation where individuals and families have limited/uncertain access to nutritionally-adequate and safe foods for healthy-living. Family is basic social-unit comprising parents and children living together in household. Household-food insecurity and family-size are risk factors for depression. However, their synergistic and/or multiplicative effect on depression are not well established. This study explored household-food insecurity, family-size and their interaction on depression prevalence among teenaged pregnant girls in Twifo-Atti-Morkwa district. Methods: WHO-STEPS multi-stage clustered-random sampling-survey was used to recruit study participants. 20-electoral areas in Twifo-Atti-Morkwa district were randomly selected, and structured-questionnaire used to collect demographic-variables. Household-Food-Insecurity Access-Scale (HFIAS) and Child-Anxiety and Depression-Scale (RCADS-25) were used to collect data. Results:Diastolic blood pressure (P-value=0.014) and household-food insecurity (P-value= 0.0001) were significant for depression. Moderate-family-size AOR=1.08, 95%CI (1.17-3.71) and large-family-size AOR2.78, 95%CI (3.98-10.19) were significant for depression. Moderate-food insecurity AOR= 0.12, 95%CI (0.41-0.35) and high-food insecurity AOR= 0.27, 95%CI (0.11-0.71) were significant for depression. Interaction between moderate-food insecurity and moderate family-size AOR=1.69, 95%CI (2.79-17.51), interaction between high-food insecurity and low family-size AOR=1.24, 95%CI (1.57-11.41) and finally, interaction between high-food insecurity and large-family-size AOR=1.01, 95%CI (1.72-14.57) were significant for depression among teenaged pregnant girls. Conclusion: There is depression prevalence among populace in Twifo-Atti-Morkwa district. Teenaged pregnant girls report moderate and high depression prevalence. Household-food insecurity, and family-size are risk factors influencing depression among teenaged girls in the district. We recommend the need for population-based public health interventions in Twifo-Atti-morkwa district, targeting teenaged pregnant girls.