Human immunodeficiency virus (HIV) is a single-stranded RNA virus that can weaken the body’s cellular and humoral immunity and is a serious disease without specific drug management and vaccine. This study aimed to evaluate the epidemiologic characteristics and transmissibility of HIV. Data on HIV follow-up were collected in Nanning City, Guangxi Zhuang Autonomous, China. An HIV transmission dynamics model was built to simulate the transmission of HIV and estimate its transmissibility by comparing the effective reproduction number (Reff ) at different stages the rapid growth period from January 2001 to March 2005, slow growth period from April 2005 to April 2011, and the plateau from May 2011 to December 2019 of HIV in Nanning City. High-risk areas of HIV prevalence in Nanning City were mainly concentrated in suburbs. Furthermore, high-risk groups were those of older age, with lower income, and lower education levels. The Reff in each stage (rapid growth, slow growth, and plateau) were 2.74, 1.62, and 1.15, respectively, which suggests the transmissibility of HIV in Nanning City has declined and prevention and control measures have achieved significant results.Over the past 20 years, the HIV incidence in Nanning has remained at a relatively high level, but its development trend has been curbed. Transmissibility was reduced from 2.74 to 1.15. Therefore, the prevention and treatment measures in Nanning City have achieved significant improvement.