Abstract Background: Serous ovarian carcinoma (SOC) is considered the most common epithelial ovarian malignancies. SOC is still having dismal outcome mainly due to early invasion, spread and resistance to chemotherapeutic agents e.g. platinum based drugs. Recent researches focused on detection of novel therapies and how to overcome chemotherapy resistance in those patients. Hypoxia inducible factor (HIF)-1 ? is the transcription factor which is the first detected mediator of cell response to hypoxia in normal and malignant cells. Tau protein (50–64 kD), which is a gene product that can bind to beta-tubulin. It was isolated from brain tissue and was associated with many neurodegenerative diseases. Aim of the study to clarify the predictive and prognostic roles of (HIF)-1? and Tau protein expression in malignant tissues of 40 patients with SOC received paclitaxel first-line chemotherapy. Methods; we have evaluated expression of HIF-1? and Tau protein expression by using immunohistochemistry in malignant tissues of forty patients of SOC. We evaluated the predictive and prognostic roles of expression of both proteins in SOC patients that have received first-line chemotherapy. We have followed patients for about three years to assess overall survival rate (OS) and resistance to chemotherapy. Results: tissue expression of HIF-1? and Tau-protein in SOC was positively correlated with advanced stage of the tumor (p=0.006& 0.002 respectively), peritoneal implants (p=0.005), higher grade of the tumor(p=0.001& 0.008 respectively), presence of distant metastases (p=0.002& 0.032 respectively), presence of ascites (p=.034& 0.046 respectively) and L.N metastases (p=0.003& <0.001 respectively), chemoresistance (p= 0.03& 0.042 respectively), recurrence of the disease after successive therapy and unfavorable survival rates (p<0.001) Conclusion: both HIF-1? and Tau-protein are markers of unfavorable outcome of SOC patients.