The Ca2+/calmodulin dependent kinase II (CaMKII) represents a family of serine/threonine kinases with diverse functions, implicated in various signalling pathways in the cell, especially in those controlling cellular proliferation and cellular death. The human epidermoid carcinoma cell line A431 is an established model for the study of the cell cycle and cancer-associated signalling, in which the role of CaMKII is not so well elucidated. Therefore, the present study aimed to investigate the role of CaMKII in the induction of apoptosis in the cell line A431 following ultraviolet (UV) irradiation and to determine the downstream events with a focus on the caspase cascade. For the latter purpose, we employed a method initially developed for the simultaneous determination of the activity of 10 different caspase enzymes. Following exposure to UV light, we observed activation of the activator caspase-8 followed by activation of the effector caspase-3, triggering apoptosis in the epidermoid carcinoma cell line A431. The results supported a pivotal role of caspases and demonstrated that a protein kinase cascade involving caspases-8 and -3 is the main pathway driven in UV-induced apoptosis in the human carcinoma cell line A431, and apoptotic stimuli triggering this pathway passed through activation of the kinase CaMKII.