HSP70 of grass carp and outer capsid protein VP7 of GCRV determines the early stage of viral entry. Multi-transcriptomic analysis identified HSP70 as a key player in the pathogenesis of GCRV infection. Temperature-dependent, and primarily plasma membrane anchored HSP70 interacts with VP7 to facilitate viral entry during the early phase of GCRV infection. We indentified the interaction of vp7 and hsp70 by MS.