Objective To elucidate the role of G2 / S phase expressed 1 (GTSE1) in carboplatin resistance mechanisms in ovarian cancer. Methods (1) GTSE1 protein expression was compared between carboplatin-sensitive (OVCAR3, OV3R-CBP, COC1) cell lines by Western blot. (2) GTSE1 was then silenced in OV3R-CBP cells using small interfering ( si) RNA transfection si-GTSE1 or si-normal control (NC), and the knockdown efficiency was confirmed by quantitative reverse transcription-polymerase chain reaction and Western blot. Carboplatin dose-response assays (0, 10, 20, 40, 80 and 160 μmol / L) were conducted to determine the half-maximal inhibitory concentration (IC50 ) and drug resistance index. (3) OV3R-CBP cells were treated with various combinations: carboplatin alone (70 μmol / L, CBP group), carboplatin plus LY2109761 ( 10 μmol / L, CBP +si+LY2109261 group), carboplatin plus si-NC (CBP +si-NC group), carboplatin plus si-GTSE1(CBP +si-GTSE1 group), and a triple combination of carboplatin, si-GTSE1 and XMU-MP-1 ( 1 μmol / L,CBP +si-GTSE1+XMU-MP-1 group). Expression levels of Ecadherin, Vimentin, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) were detected by Western blot. Cell proliferation inhibition and apoptosis were assessed by Cell Counting Kit-8 assay and flow cytometry. Results (1) GTSE1 expression was significantly elevated in OV3R-CBP relative to OVCAR3 /COC1 cells (P<0. 05). ( 2 ) Knockdown of GTSE1 significantly decreased GTSE1 mRNA/ protein levels and carboplatin IC50 and resistance index (P<0. 05). ( 3) Silencing GTSE1 in the presence of carboplatin suppressed YAP, TAZ, and Vimentin expression, and enhanced E-cadherin expression, YAP / TAZ phosphorylation, cell proliferation inhibition, and apoptosis (P<0. 05). Hippo pathway inhibition using XMU-MP-1 reversed these effects,indicating pathway-specific modulation. Conclusions Silencing GTSE1 reverses carboplatin resistance in ovarian cancer cells by activating the Hippo-YAP / TAZ pathway and inhibiting epithelial-mesenchymal transition. Targeting GTSE1 restores chemosensitivity via reactivation of the Hippo pathway, offering a potential therapeutic strategy for overcoming platinum resistance in ovarian cancer.