Taken together, these findings suggest that emodin mediated oxidative injury (DNA damage) based on ROS production and ER stress based on the levels of GADD153 and GRP78 that acts as an early and upstream change in the cell death cascade to caspase- and mitochondria-dependent signaling pathways, triggers mitochondrial dysfunction from Bcl-2 and Bax modulation, mitochondrial cytochrome c release and caspase activation, consequently leading to apoptosis in SCC-4 cells.