CMTM5 (CKLF-like MARVEL transmembrane domain-containing member 5) exhibits tumor inhibition activity with frequent epigenetic inactivation in various tumor cell lines including cervical carcinoma (CC) cells. In this paper, we examined the function of CMTM5-v1 (the primary RNA splicing form) in both HeLa and SiHa cells. Overexpression of CMTM5-v1 in both cells can induce apoptosis, but the effects are more obvious in SiHa than that in HeLa. In SiHa cells, restoration of CMTM5-v1 caused disruption of mitochondrial transmembrane potential, release of cytochrome c, activation of caspase3 and cleavage of PARP. General caspase inhibitor almost prevented apoptosis of SiHa cells, suggesting that CMTM5-v1 induces apoptosis mainly through caspase-dependent pathway. These findings verify that CMTM5-v1 inhibits the growth of CC cell lines via inducing apoptosis.