Cervical cancer, which arises in the cervical epithelial cells, is mainly caused by persistent infection with high-risk human papillomavirus. Replication factor C subunit 4 (RFC4) is instrumental in DNA replication and repair. This study elucidated the role of RFC4 in cervical cancer by Quantitative real-time PCR and western blotting were performed to confirm RFC4 mRNA and protein expression levels. Following RFC4 knockdown using small interfering RNA, cervical cancer cells HeLa, ME-180, and SiHa were assessed for cell proliferation, metastatic potential, and cell cycle distribution using MTT, colony formation, migration and invasion assays, and flow cytometry. RFC4 mRNA and protein expression was up-regulated in cervical cancer cells. RFC4 knockdown prevented cell proliferation, migration, and invasion in cervical cancer cells. Additionally, RFC4 knockdown induced cell-cycle arrest, inhibiting cell proliferation. RFC4 plays a key role in the progression and metastasis of cervical cancer cells and RFC4 may be an important therapeutic target in patients with cervical cancer.