BACKGROUND: Previous studies showed an increase in HIV prevalence among young men who have sex with men aged 25 years or younger in China. OBJECTIVE: This study aimed to assess HIV prevalence and associated factors among young men who have sex with men in the Guangxi Zhuang Autonomous Region. METHODS: This study was conducted in 4 cities (Guilin, Liuzhou, Beihai, and Nanning) in the Guangxi Zhuang Autonomous Region between June 2014 and May 2016. Participants were reached through web-based and site recruitment approaches. Laboratory tests were performed to detect HIV and syphilis infections. A self-administered questionnaire was used to collect data from 632 eligible young men who have sex with men. RESULTS: The prevalence of HIV and syphilis was 9.3% (59/632) and 11.4% (72/632), respectively. Multivariable logistic analysis showed that ethnic minority (adjusted odds ratio [AOR] for Han Chinese vs other minorities 0.28, 95% CI 0.11-0.71, P=.007), receptive sexual positioning in the past 6 months (AOR 2.94, 95% CI 1.32-6.53, P=.008), current syphilis infection (AOR for individuals without vs those with infection 0.38, 95% CI 0.19-0.75, P=.005), inconsistent condom use in the past 6 months (AOR 1.91, 95% CI 1.06-3.45, P=.03), and psychotropic drug use before last anal intercourse (AOR 16.70, 95% CI 2.34-119.18, P=.005) were independently associated with HIV infection. CONCLUSIONS: There is an urgent need to scale up HIV and syphilis interventions in young men who have sex with men. Some subgroups might need specific attention for HIV prevention, including ethnic minority men, individuals with a history of sexually transmitted infections, and individuals who have been engaging in receptive anal sex.