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The purpose of this study was to determine the cytotoxicity of the zinc-oxide eugenol-based root-canal sealer Canals on murine immortalized cementoblast cell line. Cytotoxicity judged by the alamarBlue assay demonstrated that Canals exhibited cytotoxicity to cementoblasts in a dose-dependent manner (P < 0.05). The apoptotic cell death via caspase activation was evaluated by fluorometric assay. Canals was found to stimulate caspase-3, -8, and -9 activities in a dose-dependent manner (P < 0.05). In summary, the cytotoxicity of Canals occurs through apoptosis by the activation of caspases in cementoblasts.