We have previously established an in vitro model of the earthworm Eisenia fetida and highlighted a considerable involvement of phagocytes in the cellular responses to silver nanoparticles exposure. Our in vitro model was tested in a conventional cell culture environment with serum supplements, and the primary cells were thus exposed to silver nanoparticles with pre-formed corona of serum albumin (a major serum protein). Here we have profiled proteins forming the hard corona around silver nanoparticles (OECD reference materials, 15 nm and 75 nm) using gel electrophoresis techniques to identify proteins that strongly interact with the nanoparticles. This study was accompanied by multi-parametric flow-cytometry analysis of the cellular responses, in particular nanoparticle accumulation and cytotoxicity. The formation of and differential cellular responses to nanoparticle-protein complexes underscore the need for evaluation of the protein corona in invertebrate in vitro setting.