The nonreceptor tyrosine kinase c-ABL controls cell growth but its contributions in solid tumors are not fully understood. Here we report that the Polo-like kinase PLK1, an essential mitotic kinase regulator, is an important downstream effector of c-ABL in regulating the growth of cervical cancer. c-ABL interacted with and phosphorylated PLK1. Phosphorylation of PLK1 by c-ABL inhibited PLK1 ubiquitination and degradation and enhanced its activity, leading to cell-cycle progression and tumor growth. Both c-ABL and PLK1 were overexpressed in cervical carcinoma. Notably, PLK1 tyrosine phosphorylation correlated with patient survival in cervical cancer. In a murine xenograft model of human cervical cancer, combination treatment with c-ABL and PLK1 inhibitors yielded additive effects on tumor growth inhibition. Our findings highlight the c-ABL-PLK1 axis as a novel prognostic marker and treatment target for human cervical cancers. (C) 2016 AACR.