The cellular prion protein (PrPC), altered forms of which are associated with neurological prion disorders, is overexpressed in gastric, breast, prostate, and colorectal cancer. Its overexpression affects cell proliferation, migration, and invasion, and confers resistance to chemotherapy. PrPC is a prospective target for therapeutic and biomarker development and the study of PrPC may offer new theoretical insights into cancer biology. This review explores the molecular mechanism by which PrPC overexpression contributes to the promotion of cancer. We hypothesise that PrPC may have a role in angiogenesis. We also consider the possible use of lipid nanoparticles as the therapeutic agent to target overexpressed PrPC selectively in cancer. An improved knowledge of these molecular mechanisms may reveal additional targets for cancer treatment. Further research is required to elucidate these mechanisms and to formulate targeted interventions.