Continuing our earlier study on gefitinib-mediated glioma apoptosis [22], we had found here that gefitinib-induced glioma apoptosis was parallel with the following events: elevated GRP78, ATF4, and CHOP protein expressions; PERK, eIF2α, and IRE1 protein phosphorylation; ATF6 proteolytic cleavage; free Ca2+ mobilization; and ROS generation, crucial signs of ER stress. Here, ATF6 is linked to central nervous system cancer.