BackgroundHIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the ‘CDC-Public Security Bureau-NGO’. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions.MethodsThe research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, including a 4-year traditional intervention (2014–2017) and the 4-year ‘CDC-Public Security Bureau-NGO’ innovative intervention (2018–2021), was conducted to evaluate the effects of the new intervention. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018–2021; P and C values were used to evaluate the performance of the model. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients.ResultsThe condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P < 0.05), newly reported cases of HIV have decreased by 15.56% yearly and the HIV positive detection rate among middle-aged and elderly people has dropped by 14.47%. The innovative intervention model has significantly reduced the HIV infection rates.ConclusionsThe ‘CDC-Public Security Bureau-NGO’ innovative intervention has achieved beneficial effects on HIV/AIDS prevention and control and provides a good reference for Guangxi, China.