This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor (VEGF)-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.