Cervical cancer is a growing global disease in developing countries. Persistent infection with human papillomaviruses (HPV) is an essential causative agent in this type of cancer. Several studies demonstrate HPV E5 oncoprotein can impress the normal life cycle of HPV-infected cells by targeting some pivotal cellular signaling pathways, such as the epidermal growth factor receptor (EGFR) signaling pathway. In this study, we used E5-siRNA to knockdown that essential oncogene and considered the effect of E5 silencing on proliferation, apoptosis, cell cycle, apoptosis-related gene expression, and the initiator of the EGFR signaling pathway in cervical cancer cells. The results demonstrate that E5 plays an essential role in the proliferation and inhibited apoptosis in cervical cancer. Furthermore, silencing E5 reduces proliferation, increases apoptosis, and elevates related-genes expression of these malignant cells. Overall, E5 suppression may be appropriate for ameliorating cervical cancer progression.