Objective To analyze the expression differences in immune cells and cytokines in advanced ovarian cancer with different homologous recombination deficiency (HRD) statuses, and provide insights for novel therapeutic strategies. Methods A total of 68 patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅲ-Ⅳ epithelial ovarian cancer, who were treated at Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from Jan. 2018 to Jan. 2023, were enrolled. Based on genetic testing results, patients were stratified into HRD-positive (n＝30) and HRD-negative (n＝38) groups. Baseline characteristics and clinical outcomes were compared. The expression levels of CD4, CD8 and CD25 in ovarian cancer tissues of the 2 groups were analyzed by immunohistochemical staining. The proportions of CD4⁺ T cells, CD8⁺ T cells, and CD4⁺CD25⁺ regulatory T cells (Treg cells) and CD4⁺/CD8⁺ ratio in blood were analyzed by flow cytometry. The serum levels of interferon-γ (IFN-γ), interleukin (IL)-2, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay. Results There were no significant differences in age, course of disease, family history, initial treatment, tumor FIGO stage, or tumor differentiation degree between the HRD-positive group and HRD-negative group (all P＞0.05). In terms of clinical efficacy, the objective remission rate and disease control rate of patients in the HRD-positive group were significantly higher than those in the HRD-negative group (both P＜0.05). Compared with the HRD-negative group, the expression levels of CD4, CD8, and CD25 in tumor tissues of patients were all increased in the HRD-positive group (all P＜0.05), the proportions of CD4⁺ T cells, CD8⁺ T cells, and CD4⁺CD25⁺ Treg cells in blood were all increased (all P＜0.05), the CD4⁺/CD8⁺ ratio in blood was increased (P＜0.05), the serum levels of IL-2, IL-6, and IL-10 were all increased (all P＜0.05), while the serum level of IFN-γ had no significant difference between the 2 groups (P＞0.05). Conclusion HRD-positive ovarian cancer displays enhanced tumor-infiltrating lymphocytes and immunomodulatory cytokine secretion compared to HRD-negative cases, suggesting greater sensitivity to immunotherapy and better prognosis.