Homeless individuals are at risk for numerous health problems including Hepatitis C virus (HCV). HCV is primarily caused by sharing of equipment associated with injection drug use (IDU). In the current study, we assessed differences among HCV-negative and HCV-positive homeless men residing in Los Angeles (N = 198; about 50% HCV positive) on a number of risk factors and behaviors. Findings revealed several significant correlates of HCV-positive status. HCV-positivity was significantly and positively associated with a history of substance use (IDU and non-IDU), recent IDU-related behaviors including equipment sharing, other forms of sharing (e.g., toothbrushes, razors), homelessness severity, tattoos, sexually transmitted diseases, a jail/prison history, and greater age. Lifetime alcohol problems were not associated with HCV. Although associations of HCV with current IDU-related behaviors are not surprising, it is alarming that these behaviors were recent. Those who work among homeless populations should be aware not only of the high likelihood of HCV infection in this population but also of the transmission risk due to continued IDU sharing behaviors. Substance abuse treatment should be implemented to hinder the spread of HCV in this vulnerable population. Also, needle exchange and provision of clean ancillary IDU equipment should be encouraged in areas where homeless people are known to congregate.