Objective: To investigate the effects of silencing epithelial splicing regulatory protein 1 (ESRP 1) gene expression on isoform switch of fibroblast growth factor receptor 2 (FGFR2) in ovarian cancer OVCAR5 cells. Methods: The two lentivirus expression vectors carrying ESRP1- shRNA1/2 targeting ESRP 1 gene (named as pLVTHM/ESRP1-shRNA1 and pLVTHM/ESRP1-shRNA2, respectively) were constructed, while the vector pLVTHM/ NC-shRNA was used as the negative control. The three plasmids were separately transfected into 293T cells to prepare the recombinant lentivirus, and the recombinant lentivirus carrying ESRP1- shRNA1/2 and NC-shRNA were infected into OVCAR5 cells, respectively. Then the expression levels of ESRP1 mRNA and protein in OVCAR5 cells were determined by real-Time fluorescent quantitative PCR and Western blotting, respectively. The effect of ESRP 1 gene silencing on FGFR2 isoform switch was detected by restrictive endonucleases Ava I and Hin C II The effect of ESPR 1 gene silencing on the proliferation of OVCAR5 cells was detected using MTT method. The changes of E-cadherin, N-cadherin and β-catenin expressions were detected by Western blotting. Results: The lentivirus expression vectors containing ESRP1-shRNA1/2 were constructed successfully, and their recombinant lentivirus were obtained. Compared with the negative control group, the expressions of ESRP1 mRNA and protein in OVCAR5 cells were significantly inhibited by ESRP1 shRNA (both P < 0.05). ESPR 1 gene silencing could induce the FGFR2 isoform switch from epithelial subtype (FGFR2b) to mesenchymal subtype (FGFR2c) in OVCAR5 cells, and could promote cell proliferation, down-regulate the expression of E-cadherin, up-regulate the expression of N-cadherin, and activate β-catenin in OVCAR5 cells (all P < 0.05). Conclusion: ESPR 1 gene silencing could induce the isoform switch of FGFR 2 gene switch, promote cell proliferation and induce epithelialmesenchymal transition (EMT) in OVCAR5 cells. The processes may involve the regulation of Wnt/β-catenin signaling pathway.