Food insecurity is a risk factor for both HIV transmission and worse HIV clinical outcomes. We examined the prevalence of and factors associated with food insecurity among homeless and marginally housed HIV-infected individuals in San Francisco recruited from the Research on Access to Care in the Homeless Cohort. We used multiple logistic regression to determine socio-demographic and behavioral factors associated with food insecurity, which was measured using the Household Food Insecurity Access Scale. Among 250 participants, over half (53.6%) were food insecure. Higher odds of food insecurity was associated with being white, low CD4 counts, recent crack use, lack of health insurance, and worse physical and mental health. Food insecurity is highly prevalent among HIV-infected marginally housed individuals in San Francisco, and is associated with poor physical and mental health and poor social functioning. Screening for and addressing food insecurity should be a critical component of HIV prevention and treatment programs.