Abstract: Objective: To analyze the molecular transmission network characteristics of human immunodeficiency virus (HIV)-infected individuals in Fusui County, Chongzuo City, Guangxi, and to explore the risk factors contributing to network cluster and high-risk transmission. Methods: Blood samples were collected from HIV/AIDS patients diagnosed in Fusui County between 2005 and 2021. A molecular transmission network was constructed through comparative sequence analysis of amplified HIV-1 pol sequences. Binary logistic regression was used to analyze factors influencing entry into the molecular network and high-risk transmission. Results: In this study, a total of 349 HIV-1 pol sequences were analyzed, including 6 strain subtypes from Fusui County: CRF01_AE subtype (49.86%), CRF07_BC subtype (32.38%), CRF08_BC subtype (14.33%), CRF55_01B subtype (1.14%), C subtype (0.29%), and unique recombinant form (URF) (2.00%). Among the sequences, 192 (55.01%) sequences entered the molecular transmission network, forming 31 clusters, 192 nodes, and 736 edges. Individuals aged over 50 years (aOR=1.861, 95% CI: 1.009-3.433), infected with the CRF07_BC subtype strain (aOR=4.386, 95% CI: 2.533-7.594), with education level of primary school or below (aOR=1.709, 95% CI: 1.070-2.729), with a history of non-marital commercial heterosexual contact (aOR=1.682, 95% CI: 1.027-2.753), and having a positive spouse/regular sexual partner (aOR=2.428, 95% CI: 1.181-4.995), were more likely to enter the transmission network for cluster transmission. Furthermore, individuals aged over 50 years (aOR=1.861, 95% CI: 1.009-3.433), infected with CRF07_BC (aOR=4.386, 95% CI: 2.533-7.594), and with education level of primary school or below (aOR=1.699, 95% CI: 1.004-2.874), were more likely to be high linkage transmission. Conclusion: The key population for AIDS transmission in Fusui County, Chongzuo City, Guangxi, is older adults aged over 50 years with a primary school education or below. It is important to conduct source tracing investigations based on the transmission clustering characteristics of key populations in the molecular network and implement targeted interventions to reduce secondary transmission.