ObjectiveHigh-grade serous ovarian cancer (HGSOC) is a deadly malignancy. Homeobox protein A9 (HOXA9) is linked with serous papillary histotype differentiation, and inappropriate HOXA9 expression is a step in ovarian cancer that induces aberrant differentiation. This study aimed to reveal the significance of HOXA9 in HGSOC. MethodsHOXA9 mRNA and protein expression were examined by quantitative PCR and immunohistochemistry, respectively. The chi-square test was used to evaluate associations between HOXA9 expression and clinical characteristics. The prognostic value of HOXA9 was calculated by the Kaplan-Meier method. The Kaplan-Meier Plotter database was used to assess the prognostic value of HOXA9. ResultsThe mRNA and protein expression of HOXA9 were significantly upregulated in chemotherapy-resistant HGSOC compared with chemotherapy-sensitive HGSOC. The chi-square test showed that high HOXA9 expression was significantly related with grade, clinical stage, and residual disease. High HOXA9 expression was significantly associated with poor prognosis. The Kaplan-Meier Plotter database further confirmed these results. Cox hazard regression showed that high HOXA9 expression was an independent prognostic factor for survival in HGSOC patients. ConclusionThis study showed that HOXA9 expression was associated with chemotherapy resistance and poor outcomes in HGSOC patients. High HOXA9 expression might be a prognostic indicator for HGSOC.