This study investigated the transmission patterns of tuberculosis and its associated risk factors in Hunan province to inform the development of prevention and control strategies in the region.An 8-year retrospective population-based genomic epidemiological study was conducted. Genomic clusters were defined using distance thresholds of 12-single-nucletide-polymorphisms. Risk factors associated with TB transmission were analyzed using logistic regression model. Kernel Density analysis was used to locate hotspots where transmission occurred.Among 2649 TB cases included in this study, 275 clusters were identified, with an overall clustering rate of 24.7% (654/2649). Nearly 95% (620/654) of clustered strains were isolated from the same county. Of the 275 clusters, 23 (8.4%, 23/275) had differences in drug-resistant profiles, with FQs resistance mutations occurring most frequently (52.2%, 12/23). Multivariate analysis identified male TB patients, those aged 30-60 years, ethnic minorities, non-farmers, retreated TB patients, and individuals infected with MDR/RR-TB as independent risk factors for TB transmission (P<0.05).Recent transmission in the region is predominantly occurring within counties. The risk factors related to the TB transmission and the hotspots where transmission occurs can provide a scientific basis for the formulation of targeted tuberculosis prevention and control strategies.Copyright © 2024. Published by Elsevier Ltd.