Background: Communication inequalities can affect health-seeking behaviors yet the relationship between Internet use and overall health is inconclusive. Communication-related inequalities vary by race/ethnicity and SES but existing research primarily includes middle-class Whites. We therefore examined the relationship between communication-related inequalities-measured by daily Internet use-and health-related quality of life (QOL) using a nationwide prospective cohort study in the United States that consists of primarily low income, minority women. Methods: We examined Internet use and QOL among participants in the Women's Interagency HIV Study. Data collection occurred from October 2014-September 2015 in Chicago, New York, Washington DC, San Francisco, Atlanta, Chapel Hill, Birmingham/Jackson and Miami. We used multi-variable analyses to examine the relationship between daily Internet use and QOL. Results: The sample of 1,915 women was 73% African American and 15% Hispanic; 53% reported an annual income of ≤$12,000. Women with daily Internet use reported a higher QOL at six months, as did women with at least a high school diploma, income >$12,000, and non-White race; older women and those with reported drug use, depressive symptoms and loneliness had lower QOL. Conclusions: Overcoming communication inequalities may be one pathway through which to improve overall QOL and address public health priorities. Reducing communication-related inequalities-e.g, by providing reliable Internet access-and thus improving access to health promoting information, may lead to improved health outcomes.