It is reported that intracellular accumulation of reactive oxygen species (ROS) plays a pivotal role in TNF-α-induced cell apoptosis and necrosis;however, the key molecules regulating ROS generation remain unclear.Here, we show that knockdown of endogenous receptor for activated C kinase 1 (RACK1) increases the intracellular ROS level upon TNF-α or hydrogen peroxide stimulation in human hepatocellular carcinoma (HCC) cells, thereby promoting the cell death.Carbonyl reductase 1 (CBR1), a ubiquitous NADPH-dependent enzyme, is reported to protect cells from ROS-induced cell damage.