α-Lipoic acid (LA) shows a protective effect on oxidative stress-induced apoptosis while it induces apoptosis in various cancer cells. Intracellular Ca2+ plays a central role in triggering apoptotic pathways. In the present study, we aim to investigate whether LA induces apoptosis in lung cancer cells and whether Ca2+ is involved in LA-induced apoptosis. We found that LA decreased cell viability and increased DNA fragmentation of the cells. LA activated the caspase-independent pathway, determined by upregulation of poly(ADP-ribose) polymerase (PARP) and increased the nuclear level of apoptosis-inducing factor and caspase-dependent apoptotic pathway, determined by increased levels of cytochrome c and PARP-1 cleavage product. LA-induced apoptotic alterations were inhibited in the cells treated with Ca2+ chelator BAPTA-AM. In conclusion, LA induces apoptosis through caspase-independent and caspase-dependent pathways, which is mediated by intracellular Ca2+.