BACKGROUND High-grade serous ovarian cancer (HGSOC) is the most malignant gynecologic tumor. This study reveals biomarkers related to HGSOC incidence and progression using the bioinformatics method. MATERIAL AND METHODS Five gene expression profiles were downloaded from GEO. Differentially-expressed genes (DEGs) in HGSOC and normal ovarian tissue samples were screened using limma and the function of DEGs was annotated by KEGG and GO analysis using clusterProfiler. A co-expression network utilizing the WGCNA package was established to define several hub genes from the key module. Furthermore, survival analysis was performed, followed by expression validation with datasets from TCGA and GTEx. Finally, we used single-gene GSEA to detect the function of prognostic hub genes. RESULTS Out of the 1874 DEGs detected from 114 HGSOC versus 49 normal tissue samples, 956 were upregulated and 919 were downregulated. The functional annotation indicated that upregulated DEGs were mostly enriched in cell cycle, whereas the downregulated DEGs were enriched in the MAPK or Ras signaling pathway. Two modules significantly associated with HGSOC were excavated through WGCNA. After survival analysis and expression validation of hub genes, we found that 2 upregulated genes (MAD2L1 and PKD2) and 3 downregulated genes (DOCK5, FANCD2 and TBRG1) were positively correlated with HGSOC prognosis. GSEA for single-hub genes revealed that MAD2L1 and PKD2 were associated with proliferation, while DOCK5, FANCD2, and TBRG1 were associated with immune response. CONCLUSIONS We found that FANCD2, PKD2, TBRG1, and DOCK5 had prognostic value and could be used as potential biomarkers for HGSOC treatment.