Objective: The purpose of this study was to explore the expression of Granzyme B (GZMB) and its impact on the survival and prognosis of patients with ovarian serous cystadenocarcinoma (OSC) and to evaluate whether it could be used as a potential prognostic marker for OSC. Methods: The study included 43 cases of high-grade serous ovarian cancer (HGSOC) and 415 cases of OSC. Immunohistochemical analysis was performed to assess GZMB expression in cancer tissues, and the biological functions of GZMB were explored through biometric analysis. Results: In HGSOC tissues, later Federation International of Gynecology and Obstetrics (FIGO) staging was associated with lower GZMB expression (p < 0.05). Moreover, GZMB expression was significantly related to clinical stage, distant metastasis, histological grade, and survival status (p < 0.05), whereas it was not related to age (p > 0.05). GZMB was also identified as a regulator of the immune response in the tumour microenvironment. Conclusions: GZMB is closely related to the occurrence and development of OSC, participating in immune regulation; hence, it could be a potential prognostic biomarker of OSC.