This pilot study tests the feasibility of using a Talking Circle approach and measures cultural values and beliefs within a HIV/AIDS and hepatitis C virus (HCV) prevention program conducted among a Native American (Cherokee) youth population. A descriptive correlation design was used to examine the relationship between Cherokee self-reliance and HIV/AIDS and HCV knowledge, attitudes, and behaviors. The study used three questionnaires that were administered before and after the prevention program to collect data from a convenience sample of 41 students at a public high school within the boundaries of the Cherokee Nation in Oklahoma. Statistical analysis revealed immediate differences between pretests and posttests related to knowledge, attitudes, and behavioral intentions concerning HIV/AIDS and HCV and the cultural dynamic of Cherokee self-reliance. (Contains 3 tables.)