Folate receptor alpha (FR alpha) is over-expressed in numerous epithelial malignancies, however, the association between FRa and cervical cancer remains unclear. The purpose of this study was to explore the effects of FRa on cervical cancer and its regulation of the ERK signaling pathway. In this case-control study, moderate/strong expression of FRa, phosphorylated ERK1/2(p-ERK1/2), p-c-Fos, and p-c-Jun proteins was increased with the progressive severity of cervix lesions (P < 0.05). Moreover, the expression levels of p-ERK1/2, p-c-Fos, and p-c-Jun proteins was positively correlated with those of FRa protein in cervical squamous cell carcinoma (SCC) group (P < 0.05). In vitro experiment indicated down regulation of FRa by siRNA suppressed cell proliferation, promoted cell apoptosis, induced cell cycle arrest at G0/G1 phase, and reduced expression of p-ERK1/2, p-c-Fos, and p-c-Jun proteins. The results suggest that FRa is associated with the progression of cervical cancer and regulates cervical cancer cells growth through phosphorylating ERK1/2, c-Fos, and c-Jun, which are key factors of the ERK signaling pathway. Therefore, FRa may be an effective target for early detection and therapy of cervical cancer. (C) 2017 Elsevier Inc. All rights reserved.