Introduction: The relationship between social support, depression, coping and health seems to be especially important for people living with HIV. The objective was to analyze the association between quality of life and family functionality in patients living with the HIV / AIDS virus at the Hospital General de Zona N. 1 in Oaxaca de Juárez. Material and methods: A descriptive, cross-sectional and retrospective study was carried out in 230 patients from the HIV clinic of the HGZ No. 1 of the IMSS Oaxaca. HIV-positive patients, adults, beneficiaries and who agreed to participate were included. Two validated surveys were applied: family functionality (family APGAR) and Health-related quality of life (MOS-HIV-SF30). A univariate and bivariate analysis was performed, with parametric and non-parametric tests (ANOVA / Kruskal Wallis, Student’s T / UMann Whitney and χ². Results: 85.2% of the people were men, with an average age of 39 ± 14.3 years. The time of evolution of the diagnosis was 7 ± 2.6 years. The perception of quality of life regarding health in PLWHA was 83%, the degree of family dysfunction was 32.2% in PLWHA. There is a directly proportional relationship between health-related quality of life (HRQL) and family functionality (p ≥ 0.05). Discussion: From the point of view of family medicine, HIV / AIDS is a complex process that goes beyond a health crisis. It is not only an attempt to face a biological ailment, but also to confront psychological fears, social reactions, ignorance, prejudice and discrimination, even from the family. PLWHA must seek and have psychotherapeutic support and great family support to be able to assume the disease.