Globally, ovarian cancer (OvCa) is the deadliest gynecological malignancy, which threatens women's health.1 Despite innovations in cancer treatments, nearly 70% of OvCa patients still suffered tumor recurrence and poor survival after standard therapy.1 Therefore, further research is urgently needed to identify prognostic biomarkers and explore specific mechanisms for OvCa. Tertiary lymphoid structure (TLS), a newly acknowledged form of ectopic lymphoid tissues, plays a crucial role against cancer, though have not been validated in OvCa yet.2 Here, we developed and validated a TLS-related gene (TRG) signature to predict drug sensitivity and prognosis for OvCa patients via bioinformatics analysis. Moreover, through PCR and multiplex immunohistochemical analyses, we validated the importance of TLS and the related signature, particularly STAT5A (signal transducer and activator of transcription 5 A), thus assisting clinical decision-making for OvCa precision treatment.