The aim of our study is to examine the effect of extracellular ATP whether it is correlated with intracellular Ca concentrations ([Ca2+]i) on human liver hepatocellular cells (HepG2). The extracellular ATP is responsible for regulating both cells signaling and cell functions. ATP maintains these effects through purinergic P2 receptors. The extracellular ATP promotes the release of Ca2+ from the Ca2+ stores to the cytoplasm in the cell and increases [Ca2+] I in the cell. In our study, various concentrations of ATP (10-3M-10-7M) were applied to HepG2 cells and incubated for 24 hours, 48 hours, and 72 hours. At these concentrations, the proliferation of cells and apoptosis of the cells was examined for 24 hours, 48 hours, and 72 hours. Similarly, cells with different ATP concentrations incubated for 24 hours and 48 hours were loaded with Indo 1FF AM calcium indicator to measure [Ca2+]i. Surprising results were obtained, 10-6M-10-7M extracellular ATP was found to be more toxic than 10-3 M-10-4 M extracellular ATP, (p<0.05). Low concentrations of ATP also reduced [Ca2+]i for 24 hours and 48 hours of incubations (p<0.01). As a result, low concentration extracellular ATP is more toxic in HepG2 cells. At the same time, the extracellular ATP correlates with [Ca2+]i.