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The prevalence of CRF07_BC is 39.7% and has become the most infectious HIV strain in China. To study the transmission and diffusion trajectory of CRF07_BC in China and to prevent further expansion of its transmission. A total of 16,635 sequences of the CRF07_BC pol gene were collected from 1997-2020. We characterized the gene subtypes according to a phylogenetic tree analysis. A 0.50% molecular network was constructed to analyze the transmission relationship among different provinces for CRF07_BC and its two epidemic clusters. Spatial and temporal propagation characteristics were analyzed according to phylogeographic analysis. Finally, we evaluated the differences in transmission of CRF07_BC-O, and CRF07_BC-N. Our dataset included 8,816 sequences of CRF07_BC-N and 7,819 sequences of CRF07_BC-O. There were 7,132 CRF07_BC sequences in the molecular network, and the rate of clustered was 42.9%. Compared to CRF07_BC-O, CRF07_BC-N showed significantly (P <0.001) higher transmission-specific rates. CRF07_BC originated among injecting drug users (IDUs), and spread to men who have sex with men (MSMs) and heterosexual individuals (HETs), while MSMs also transmitted directly to HETs. CRF07_BC-O and CRF07_BC-N were prevalent in Xinjiang and Sichuan, respectively, before spreading interprovincially. In modern China, CRF07_BC-N occurs in five of the major economic zones. The CRF07_BC strain, which has contributed to the highest number of HIV infections in China, is divided into two epidemic clusters. Compared with CRF07_BC-O, risk of transmission is much greater in CRF07_BC-N, which is predominantly prevalent in economically developed provinces, and both MSMs and IDUs have transmitted this epidemic cluster to HETs. High-resolution, large-scale monitoring is a useful tool in assessing the trend and spread of the HIV epidemic. The rapidly developing economy of China requires an equally rapid response to the prevention and control of infectious diseases. [ABSTRACT FROM AUTHOR]