Background: Neuroendocrine carcinoma (NEC) is a rare disease, and therapy for this malignant tumor is controversial. Conventionally, platinum doublet chemotherapy has been used for advanced gastroentero-pancreatic (GEP) neuroendocrine carcinoma (GEP- NEC), but the efficacy of molecular-targeted drugs for GEP-NEC is unknown. In this study, we investigated the antitumor effect of molecular-targeted drugs on colorectal neuroendocrine carcinoma cells. Materials and methods: A colonic neuroendocrine carcinoma cell line COLO320 was treated with molecular-targeted drugs, and cell growth suppression and apoptosis induction were evaluated. Results: The cytostatic effects of molecular-targeted drugs against COLO320 were higher in the order of sorafenib, sunitinib, rapamycin, and imatinib. Flow cytometry analysis showed that sorafenib induced G1 cell cycle arrest and a high rate of apoptosis. Sunitinib showed condensation and fragmentation of nuclear chromatin, but also necrosis with cell swelling. In contrast, sorafenib strongly induced apoptosis via condensation and fragmentation of nuclear chromatin. Sorafenib-induced apoptosis was due to caspase-3 activation, and this apoptosis was inhibited with a caspase inhibitor. Conclusion: Sorafenib induces apoptosis in COLO320 cells and is a potential therapeutic agent for colonic neuroendocrine carcinomas