Laser irradiation has been recognized as a promising tool across a number of biomedical applications. However, understanding the molecular mechanisms and cellular responses remains incomplete. Here, we investigated the mechanism involved in the apoptotic process in human hepatic cells under laser irradiation. Our data show that the laser-mediated alternation of mitochondrial membrane potential leads apoptosis in Huh7 and Alexander cells. Contrary, HepG2 cells are resistant to laser induced cell death. The observed link between mitochondrial membrane potential and cytotoxicity could be a fundamental phenomenon in laser-induced cell apoptosis.