Apoptosis is of crucial importance in the life of multicellular organisms. In holometabolous insects, particularly in Lepidoptera, apoptosis is essential in biological processes such as metamorphosis and defense against pathogens. Apoptosis is tightly regulated and involves many proteins, among them caspases, which play a central role. In mammals, almost 300 targets of caspases have been described, and the expression of more than a hundred proteins has been shown to be altered in apoptotic cells. To date, the molecular pathways controlling apoptosis are poorly understood in Lepidoptera. Here, we used a comparative approach aiming to identify candidate proteins potentially implicated in these pathways. We examined changes occurring, in the proteome of a Helicoverpa armigera-derived cell line, upon induction by actinomycin D. We identified 13 proteins for which the relative abundance was significantly altered. Among these, the abundance of procaspase-1 decreased in apoptotic cells, reflecting its processing into the active form. We characterized its properties by heterologous expression and correlated the observed substrate specificity with changes in caspase activity in HaAM1 cells after induction. We also identified three chaperones as well as several putative pro- and anti-apoptotic proteins. Altogether, these data suggest that apoptotic pathways in Lepidoptera share similarities with the ones described in mammals.