Background: Food insecurity can have poor physical and mental health consequences for all family members. The present study investigated the prevalence of household food insecurity and its predictive role on the health of mothers of children aged under 60 months in Qazvin (Iran). Methods: A cross-sectional study was carried out between January 2019 and December 2020. Participants included all mothers with children aged under 60 months who referred themselves to comprehensive health centers in Qazvin (N = 1750; mean age 30.61 years). Convenience sampling was performed. Data were collected using a demographic information checklist, the General Health Questionnaire (GHQ) and the Household Food Insecurity Access Scale (HFIAS). Data analysis was performed using independent t-tests, one-way analyses of variance, uni-variable and multivariable linear regression with a significance level of p < 0.05. Results: Two-thirds of the participants had a secure food status (68.4%). Household food security status showed a significant, and inverse relationship with general health subscales. General health subscales of depression (standardized mean difference or SMD: −1.24 [95% CI: −1.36; −1.13]), somatic symptoms (SMD: −0.92 [95% CI: −1.03; −0.81]) and anxiety and insomnia (SMD: −0.72 [95% CI: −0.83; −0.61]) were significantly lower among food secure participants vs. food insecure participants. Social dysfunction was not significantly associated with household food security. The regression models demonstrated that household food security was a significant predictor for the health of mothers with children aged under 60 months: uni-variable (β = −0.38) and multivariable (β = −0.41). Conclusion: Household food security is associated with various aspects of mothers’ health. Since the growth and development of a healthy child depends on having a healthy mother, the food security situation of the family and the general health of mother can be assessed as part of providing health service regarding monitoring growth and development of children. This will help in targeting appropriate interventions if needed.