Homeless adults have high rates of hepatitis C virus infection (HCV) and low levels of HCV knowledge. This study reports results of an interdisciplinary, community-based intervention using stakeholder cooperation, case management, risk factor identification, and modification of dysfunctional psychosocial factors to increase HCV knowledge among homeless adults (N = 747). Data are from a randomized quasi-experimental study, with the major goal of evaluating the effectiveness of a Nurse Case Managed Intervention compared to a Standard Intervention, encouraging completion of a three-series hepatitis A/hepatitis B vaccination program. Increased HCV knowledge was measured with an 18-item questionnaire discerning risk factors for HCV and common misconceptions about individuals with HCV. A significant increase in HCV knowledge resulted regardless of intervention format. Receiving the Nurse Case Managed Intervention predicted greatest gain in HCV knowledge (p < 0.000). Successfully engaging key stakeholders, outreach workers, community organizations, and homeless people themselves proved most efficacious in increasing HCV knowledge.