Background: Exposure of women to socioeconomic risks, as becoming the head of the family, could influence their life quality. Therefore, assessment of women's needs in families headed by women (FHW)to achieve equity regarding health-related quality of life (HRQoL) is pivotal for stakeholders involved in women's programs. Objective: to identify the predictors of HRQoL of young women heading their families versus young wives in families headed by men (FHM). Methods: A community-based cross-sectional study compared the HRQoL for two groups of women (age is 25-49 years); 200women heading their families (group 1) and 200 wives in FHM (group 2). The study was conducted in a randomly selected shiakha (El-Atrees Shiakha) in El-Saida Zeinab district in Cairo, Egypt using structured interview questionnaire form. Results: Women heading their families who had significantly (p< 0.05) lower mean HRQoL score compared to wives in FHM were those ≥35 years old, non-educated and those with history of early marriage (mean HRQoL scores ± standard deviations were 3.5±0.6, 3.5±0.56, 3.4±0.6 respectively). Conclusion: women having socioeconomic risks related to ‘non-education, young age at marriage and working in unstable jobs" were more vulnerable to suffer from low HRQoL upon exposure to the socioeconomic crises of becoming the head of the family.