TNF and hepatocellular carcinoma: In summary, our data provides the strong evidence to support the notion that extracellular Ca2+ influx induced by TNFα facilitates the TNFα-mediated extrinsic apoptosis through activating calpain/IAPs/caspase3 signaling pathway and suggests that increasing the level of cytosolic Ca2+ might be an alternative strategy to improve the pro-apoptotic activity of TNFα in HCC cells, although suitable chemical or biological reagents need to be further tested.