The self-assembled layered adsorption of proteins onto nanoparticle (NP) surfaces, once in contact with biological fluids, has been termed the ‘protein corona’ and it is gradually seen as a determinant factor for the overall biological behavior of NPs. Here, we describe the previously unreported in vivo protein corona formed in human systemic circulation. The human-derived protein corona formed onto PEGylated doxorubicin-encapsulated liposomes (Caelyx®) was thoroughly characterized following the recovery of liposomes from the blood circulation of ovarian carcinoma patients. In agreement with our previous investigations in mice, the in vivo corona was found to be molecularly richer in comparison to its counterpart ex vivo corona. The intravenously infused liposomes were able to scavenge the blood pool and surface-capture low molecular weight, low abundant plasma proteins that could not be detected by conventional plasma proteomic analysis. This study describes the previously elusive or postulated formation of protein corona around nanoparticles in vivo in humans and illustrates that it can potentially be used as a novel tool to analyze the blood circulation proteome.