While research has begun addressing food insecurity (FI) in HIV-positive populations, knowledge regarding FI among individuals living with HIV-hepatitis C virus (HCV) co-infection is limited. This exploratory study examines sociodemographic, socioeconomic, behavioral, and clinical factors associated with FI in a cohort of HIV-HCV co-infected individuals in Canada. We analyzed longitudinal data from the Food Security and HIV-HCV Co-infection Study of the Canadian Co-infection Cohort collected between November 2012-June 2014 at 15 health centres. FI was measured using the Household Food Security Survey Module and classified using Health Canada criteria. Generalized estimating equations were used to assess factors associated with FI. Among 525 participants, 59 % experienced FI at their first study visit (baseline). Protective factors associated with FI (p < 0.05) included: enrolment at a Quebec study site (aOR: 0.42, 95 % CI: 0.27, 0.67), employment (aOR: 0.55, 95 % CI: 0.35, 0.87), and average personal monthly income (aOR per $100 CAD increase: 0.98, 95 % CI: 0.97, 0.99). Risk factors for FI included: recent injection drug use (aOR: 1.98, 95 % CI: 1.33, 2.96), trading away food (aOR: 5.23, 95 % CI: 2.53, 10.81), and recent experiences of depressive symptoms (aOR: 2.11, 95 % CI: 1.48, 3.01). FI is common in this co-infected population. Engagement of co-infected individuals in substance use treatments, harm reduction programs, and mental health services may mitigate FI in this vulnerable subset of the HIV-positive population.Electronic supplementary materialThe online version of this article (doi:10.1007/s10461-016-1326-9) contains supplementary material, which is available to authorized users.