Cervical cancer continues to be a concern, and the prognosis of locally advanced cervical cancer remains poor.IMPA2was previously identified as a potential oncogene and regulator of tumor apoptosis. In this study, we aim to further elucidate the underlying mechanisms ofIMPA2gene in the regulation of cervical cancer apoptosis. First, we identifyAIFM2as an upregulated gene inIMPA2-silenced cervical cancer cells, and inhibition ofAIFM2reversesIMPA2knockdown-induced apoptosis. Further study reveals thatAIFM2regulates cell apoptosis in a mitochondrial-dependent manner with a redistribution of mitochondrial membrane potential and intracellular Ca2+levels. However, the analysis of the STRING database and our experimental results show thatAIFM2has little effect on cervical cancer progression and survival. Further mechanistic study demonstrates thatIMPA2andAIFM2silencing inhibits apoptosis by activating p53. Meanwhile, the knockdown ofIMPA2enhances the chemosensitivity of cervical cancer cells by strengthening paclitaxel-induced apoptosis. Based on the above results, the IMPA2/AIFM2/p53 pathway may be a new molecular mechanism for paclitaxel treatment of cervical cancer and an effective strategy to enhance the sensitivity of cervical cancer cells to paclitaxel. Our findings display a novel function ofIMPA2in regulating cell apoptosis and paclitaxel resistance mediated by a disturbance ofAIFM2andp53expression, potentially making it a novel therapeutic target for cervical cancer treatment.