Cell viability assays performed on two CD44-positive cell models, namely normal human umbilical vein endothelial (HUVEC) and prostate tumor (PC-3) cells, in comparison with neuroblastoma cells (SH-SY5Y), which do not express the CD44 receptor, demonstrated an increased cytotoxicity in neuroblastoma compared to prostate cancer cells upon the cellular treatments by HA–AuNP compared to the bare AuNP, but a receptor-dependent perturbation effect on cytoskeleton actin and lysosomal organelles, as detected by confocal microscopy. The gene discussed is CD44; the disease is prostate cancer.