The study aimed to investigate the roles of gold nanoparticles (GNPs) and graphene oxide flakes (GOFs) as phagocytosis enhancers against cancer cells. The nanomaterials were characterized through SEM and UV-VIS absorptions. The GNPs and GOFs increased the macrophages’ phagocytosis ability in engulfing, thereby annihilating the cancer cells in both in vitro and in vivo conditions. The GNPs and GOFs augmented serine protease class apoptotic protein, granzyme, passing through the aquaporin class protein, perforin, with mediated delivery through the cell membrane site for the programmed, calibrated, and conditioned cancer cells killing. Additionally, protease inhibitor 3,4-dichloroisocoumarin (DCI) significantly reduced granzyme and perforin activities of macrophages. The results demonstrated that the GOFs and GNPs increased the activation of phagocytic cells as a promising strategy for controlling cancer cells by augmenting the cell mortality through the granzyme-perforin-dependent mechanism.