Objectives This study aimed to analyze sentinel surveillance data of the men who have sex with men (MSM) in the Pearl River Delta region, Guangdong province, from 2016 to 2024 to investigate the epidemiological trends of HIV and syphilis prevalence, as well as AIDS-related knowledge and sexual behaviors among MSM, and to further provide evidence for developing targeted HIV prevention and control strategies.

Methods We collected behavioral surveillance data and serological test results from MSM recruited through venue-based sampling, internet recruitment, and respondent-driven sampling methods. Temporal trends were analyzed using χ² trend tests.

Results  Among 23 236 MSM surveyed from 2016 to 2024, HIV prevalence fluctuated between 5.60%～9.98% (χ_trend²=31.843, P＜0.001), with the highest infection rate among MSM aged ≥45 years. Syphilis prevalence increased from 4.59% to 5.35% overall (χ_trend²=14.464, P＜0.001), with a similar increasing trend (2.81% to 5.56%) among young MSM aged 16～24 years (χ_trend²=17.132, P＜0.001). AIDS knowledge awareness improved from 88.62% to 95.46% during the study period (χ_trend²=134.721, P＜0.001). However, among young MSM aged 16～24 years, there was no statistically significant difference in the trend of the knowledge awareness rate regarding two points: that HIV infection could not be judged by appearance (χ_trend²= 2.504, P=0.114)and that other sexually transmitted infections (STIs) would increase the risk of HIV infection (χ_trend²=0.452, P=0.502). Condom use during sex (both homosexual and heterosexual) in the past 6 months showed overall improvement (both P<0.05), while condom use during homosexual anal sex among MSM aged 16～24 years indicated no statistically significant difference in the changing trend over years (χ_trend²=3.476, P=0.062).

Conclusion The study revealed persistently high HIV prevalence and ongoing syphilis transmission among MSM, particularly in the 16～24 and ≥45 age groups. Although AIDS knowledge improved across each age group, specific knowledge gaps persist among young MSM aged 16～24, regarding HIV/STI co-infection risks and disease manifestations. The persistence of high-risk sexual behaviors, especially among young MSM. There is an urgent need to implement full-scale, precision-oriented interventions targeting both young and middle-aged/elderly MSM. Meanwhile, efforts should be made to deepen the transformation of HIV prevention and control strategies from traditional health education to a model integrating "behavioral facilitation and structural intervention", and thereby help reduce high-risk behaviors and establish accurate health cognition.