We investigated the effects of silver nanoparticle (AgNP) and cisplatin (CiSP) exposure via the activation of TRPM2 cation channels in glioblastoma (DBTRG-05MG) cell line. The cells were divided into four groups as control, AgNPs (100 μg/ml for 48 h), CiSP (25 μM for 24 h), and CiSP + AgNPs. We found that the cytotoxic, oxidant and apoptotic actions of CiSP were further stimulated through the activation of TRPM2 (via ADP-ribose and HO) in the cells by the treatment of AgNPs. The actions were decreased in the cells by the treatments of TRPM2 antagonists (ACA and 2APB). The apoptotic actions of AgNPs were induced by the stimulation of propidium iodide positive DBTRG-05MG rate, caspase -3, caspase -8, and caspase -9 activations, although their oxidant actions were acted by the increase of mitochondrial membrane depolarization, lipid peroxidation, mitochondrial oxygen free radicals (ROS), and cytosolic ROS, but the decrease of total antioxidant status, glutathione, and glutathione peroxidase. The accumulation of cytosolic free Ca and Zn into mitochondria via the activation of TRPM2 current density and activity accelerated oxidant and apoptotic actions of AgNPs in the cells. We found that the combination of AgNPs and CiSP was synergistic via the stimulation of TRPM2 for treatment of DBTRG-05MG cells. The combination of AgNPs and CiSP showed a favorable action via the stimulation of TRPM2 in the treatment of glioblastoma tumor cells.