BackgroundOvarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC.MethodsTCGA and tissue microarrays with immunohistochemical staining (IHC) were used to examine CEBPG expression in OC. A variety of in vitro assays were conducted, including colony formation, proliferation, migration, and invasion. The orthotopic OC mouse model was established for in vivo studies. Ferroptosis was detected by observing mitochondrial changes with electron microscopy, detecting ROS expression, and detecting cell sensitivity to drugs by CCK8 assay. The interaction between CEBPG andSLC7A11was confirmed by CUT&Tag and dual luciferase reporter assays.ResultsA significantly higher expression level ofCEBPGin OC when compared with benign tissues of ovary, and that highCEBPGexpression level was also tightly associated with poor prognosis of patients diagnosed with OC, as determined by analysis of datasets and patient samples. Conversely, knockdown ofCEBPGinhibited OC progression using experiments of OC cell lines and in vivo orthotopic OC-bearing mouse model. Importantly, CEBPG was identified as a new participator mediating ferroptosis evasion in OC cells using RNA-sequencing, which could contribute to OC progression. The CUT&Tag and dua luciferase reporter assays further revealed the inner mechanism that CEBPG regulated OC cell ferroptosis through transcriptional control ofSLC7A11.ConclusionsOur findings established CEBPG as a novel transcriptional regulator of OC ferroptosis, with potential value in predicting clinical outcomes and as a therapeutic candidate.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-023-04136-0.