HBV causes ~55% of HCC. HBV integration into hepatocyte genome always precedes HCC development. We identified the initial (earliest) sites of HBV integration, and time and mechanism of merges formation. Hepatocytes exposed to HBV or WHV were analyzed from 15 min p.i. and woodchuck liver biopsies at 1 and 3 h p.i. Virus-host fusions were identified by inverse-PCR and clonal sequencing. First fusions occurred within 15 min p.i. and were in 95% head-to-tail joints implying non-homologous end joining (NHEJ). Retrotransposons were frequent initial targets. Several host genes were joined with HBV enhancer II possibly affecting hepatocyte function and oncogenesis. Their formation coincided with induction of oxygen radicals, cell DNA damage, and activation of the poly(ADP-ribose) polymerase1-mediated DNA repair machinery. Thus, HBV and WHV integrate instantly even before replication is evident. Virus-host fusions are primarily due to repair of cellular double-stranded DNA damaged by virus-triggered oxidative stress. Insertions into sequences with translocation potential suggest that HBV DNA may spread across hepatocyte genome instantly after virus entry.