A respondent-driven sampling survey was conducted to investigate HIV related serological and behavioral characteristics of men who have sex with men (MSM) in Guangzhou, China, and to identify associated factors potentially driving the epidemic. Respondent-Driven Sampling Analysis Tool and SPSS were used to generate adjusted estimates and to explore associated factors. Three hundred seventy-nine eligible participants were recruited. The adjusted prevalence of HIV and current syphilis infection are 5.2% and 17.5% respectively. 60.3% have unprotected anal sex in the past 6 months. Unprotected anal sex, having receptive anal sex and current syphilis infection are significant factors associated with HIV infection. The potential for a rapid rise of HIV and syphilis infections among MSM in Guangzhou exists. Targeted interventions with voluntary counseling and testing (VCT) and sexually transmitted infection (STI) services are needed to address the epidemic, with a focus on such subgroups as those of with current syphilis, and non-official Guangzhou residence status.