This study investigated the epidemiological and clinical characteristics of hepatitis B virus (HBV) in HIV-infected adults at the time of antiretroviral therapy (ART) initiation in Guangdong province of China. A total of 2793 HIV-infected adults were enrolled between January 2004 and September 2011. Demographic data and laboratory parameters were collected, HBV-DNA levels were measured, and HBV genotypes were identified before ART. The prevalence of hepatitis B surface antigen (HBsAg) in HIV-infected patients was 13.2%. A total of 266 HIV/HBV co-infected patients and 1469 HIV mono-infected patients were recruited. The median alanine aminotransferase and aspartate aminotransferase levels of HIV/HBV co-infected patients were higher than HIV mono-infected patients (32 U/L vs. 22 U/L, p < 0.001 and 35 U/L vs. 24 U/L, p < 0.001, respectively), whereas the median CD4 cell count of HIV/HBV co-infected patients was lower than HIV mono-infected patients (59 cells/mm³ vs. 141 cells/mm³, p < 0.001). The level of CD4 cell count was lower in hepatitis B e-antigen (HBeAg)-positive co-infected patients than HBeAg-negative patients (36 cells/mm³ vs. 69 cells/mm³, p = 0.014). Similar result was found in high level of HBV-DNA and low level of HBV-DNA groups (33 cells/mm³ vs. 89 cells/mm³, p < 0.001). HBV genotypes were classified as genotypes B and C. Patients infected with genotypes B and C differed significantly in terms of proportion of HBeAg-positive (40.5% vs. 62.2%, p = 0.014). This study indicates a high prevalence of HBsAg in HIV-infected adults in Guangdong. The level of CD4 cell count in HIV/HBV co-infected patients was much lower than HIV mono-infected patients, especially in patients with HBeAg-positive and high level of HBV-DNA. The predominant HBV genotype in HIV/HBV co-infected patients is genotype B.