Programmed cell death (PCD) is essential for normal development and reproduction which is also induced by various biotic or abiotic stresses including aluminum (Al) stress. Little is known about mechanisms of PCD induced by Al stress. In the present study, biochemical and physiological features of Cryptococcus humicola were examined under Al stress. Reactive oxygen species (ROS) accumulation and activation of caspase-3-like protease were observed in cells treated by Al stresses. DAPI staining showed a nucleus aggregation in the cell edge, nuclear chromatin condensation displaying a crescent-shaped distribution around the nucleus. Mitochondrial membrane potential (ΔΨm) and mitochondrial cytochrome c (cyt c) content were decreased after Al stress. Cyt c gene expression profiles analysis showed that the gene was up-regulated by Al stress. In summary, the physiological and molecular analysis revealed that the cyt c and caspase-3-like protease involved in the yeast apoptosis process triggered by Al stress. These results help understand the physiological mechanisms of Al stress-induced PCD process in yeast.