In one of our recent studies, two HCV genotype 6 variants were identified in patients from Hong Kong and Guangxi in southern China, with injection drug use and HIV-1 co-infection. We report the complete genomic sequences for these two variants: GX004 and HK6554. Their entire genome lengths were 9,468 and 9,462 nt; the 5′ UTRs were 338 nt followed by single ORFs of 9,069 nt; the 3′ UTRs were 61 and 55 nt including 29 and 23 nt poly(U) tracks. Phylogenetic analysis using a maximum likelihood method showed that HK6554 was classified into subtype 6g and GX004 represented the first complete genome sequence for subtype 6e. Further analysis with reference sequences in three different genomic regions revealed that GX004 closely clustered with a group of subtype 6e variants, which were previously exclusively found in Vietnam and recently increasingly identified in injection drug users from the Guangxi province in southern China that borders Vietnam. This suggests that subtype 6e could become epidemic in southern China by network transmission among injection drug users. J. Med. Virol. 78:1061–1069, 2006. © 2006 Wiley-Liss, Inc.