Background: End-stage liver disease and hepatocellular carcinoma due to hepatitis C virus (HCV) co-infection are increasingly common causes of death among HIV-infected individuals. However, there are few clinical investigations of HIV/HCV co-infected individuals from low and middle-income nations. Here, we compare the epidemiology of HCV-infected and HIV/HCV co-infected individuals in Southern China and examine hepatic fibrosis scores in co-infected individuals. Methods: We conducted a retrospective cross-sectional study of treatment-naïve HIV/HCV co-infected and HCV mono-infected subjects. Bivariate and multivariate models were used to examine the association between demographics and HCV genotype. Among co-infected individuals, we also studied the relationship between fibrosis scores derived from non-invasive studies and HCV genotype. Results: Data were collected from 175 HCV-infected individuals, including 89 (51 %) HIV/HCV co-infected individuals. HIV/HCV co-infection was correlated with intravenous drug use (AOR 46.25, p < 0.001) and not completing high school (AOR 17.39, p < 0.001) in a multivariate model. HIV/HCV co-infected individuals were more likely to be infected with HCV genotype 6a (p < 0.0001) or 3a (p < 0.023), whereas increased fibrosis (FIB-4 score) was associated with HCV genotype 3a infection (β 2.18, p < 0.001). Discussion: Our results suggest that intravenous drug use is driving HIV/HCV co-infection in Southern China. While additional studies are needed, HCV genotype 6a is more common and genotype 3a appears to be associated with more severe hepatic fibrosis in co-infected individuals. Conclusions: Future HIV/HCV co-infection research in China should focus on at risk populations, HCV testing uptake, and genotype-specific treatment.