C-X-C motif chemokine ligand 5 (CXCL5), an important chemokine, has been validated to promote human tumorigenesis. However, the clinical significance and the underlying molecular mechanisms of CXCL5 have not been completely explored in cervical cancer. Herein, the aim was to investigate miR-577-mediated CXCL5 signaling in cervical tumorigenicity.Sixty-one pairs of cervical cancer specimens and para-carcinoma tissues were collected to measure miR-577 and CXCL5 expression levels. miR-577 mimics and/or si-CXCL5 were transfected into cervical cancer cell lines, Hela, and SiHa cells, to determine their effect on cell proliferation, migration and apoptosis.Our results demonstrated that CXCL5 is overexpressed in cervical cancer tissues and cell lines. Knockdown of CXCL5 with specific siRNA transfection in Hela and SiHa cells significantly inhibited cell proliferation and migration and induced apoptosis in vitro. We also report that CXCL5 is a direct target of miR-577. Additionally, transfection of miR-577 mimics can inhibit CXCL5 protein expression, but not mRNA in Hela cells. miR-577 mimic transfection significantly inhibits migration and induces apoptosis in Hela and SiHa cells. However, the antineoplastic activities of miR-577 are reversed by overexpression of CXCL5 in vitro.Overexpression of CXCL5 is involved in tumor development of cervical cancer. Inhibition of CXCL5 by its post-transcriptional regulator, miR-577, may provide a promising therapeutic strategy for patients with cervical cancer.