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Background: Colorectal carcinoma (CRC) treatment remains severe. Survivin is aberrantly overexpressed in CRC tissues and might be a potential target for CRC treatment. TDB-6 is a new taspine derivative. The purpose of this study is to investigate the inhibitory effect of TDB-6 on CRC and its underlying mechanism., Methods: The MTT assay and xenograft model were utilized to investigate the inhibitory effect of TDB-6 on LoVo cells in vitro and in vivo . Hoechst staining and Annexin-V FITC/PI analysis were conducted to study the effect of TDB-6 on LoVo cell apoptosis. Mitochondrial membrane potential (Δψm) assay was conducted to demonstrated whether TDB-6 could induce mitochondrial-mediated apoptosis of LoVo cells. Western blotting was conducted to investigate the effect of TDB-6 on survivin protein and caspase/Bcl-2/Cyto-C signaling., Results: The results indicated that TDB-6 induced mitochondria-mediated apoptosis and inhibited the proliferation and growth of LoVo cells in vitro and in vivo . Mechanistic investigation utilizing western blotting indicated that TDB-6 inhibited survivin protein expression, and the inhibitory effect was augmented by TDB-6 and YM-155 co-administration, which revealed that TDB-6 might induce apoptosis of LoVo cells by targeted regulation of survivin. TDB-6 also regulated survivin downstream signaling. It significantly increased the protein level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, cleaved-PARP, and Cyto-C, and decreased the protein level of Bcl-2., Conclusions: TDB-6 might be a promising survivin inhibitor with great potential for CRC treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-780/coif). All authors report that this work was supported by the Key Scientific Research Project on Inheritance and Innovation of Traditional Chinese Medicine and Development of Qin Medicine (No. 2021-02-zz-015), the Natural Science Foundation of Shaanxi Province (No. 2022JM-605), and the Talent Support Program in Shaanxi Provincial People’s Hospital (No. 2021JY-29). The authors have no other conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)