Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis. This study reveals that hypoxia increases ZEB1 expression in cervical squamous cell carcinoma (CSCC) cells, which enhances CD47 and SIRPα expression, enabling cancer cells to evade phagocytosis by macrophages and promoting tumor progression. ZEB1 directly activates CD47 transcription in hypoxic CSCC cells and is enriched in exosomes derived from these cells, which transfer ZEB1 to macrophages, promoting SIRPα⁺ TAM polarization. Exosomal ZEB1 retains transcriptional activity and activates the STAT3 signaling pathway, reprogramming SIRPα⁺ TAMs. STAT3 inhibition reduces the polarizing effect of exosomal ZEB1, while ZEB1 knockdown increases phagocytosis of CSCC cells by macrophages. These findings suggest that hypoxia-induced ZEB1 strengthens the CD47-SIRPα axis, promoting immune evasion in CSCC. Targeting ZEB1 in combination with CD47-SIRPα checkpoint immunotherapy may improve outcomes for CSCC patients by disinhibiting innate immunity. The study highlights the role of ZEB1 in hypoxic tumor microenvironment and provides new insights into the mechanisms of immune evasion in cervical cancer.Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis. This study reveals that hypoxia increases ZEB1 expression in cervical squamous cell carcinoma (CSCC) cells, which enhances CD47 and SIRPα expression, enabling cancer cells to evade phagocytosis by macrophages and promoting tumor progression. ZEB1 directly activates CD47 transcription in hypoxic CSCC cells and is enriched in exosomes derived from these cells, which transfer ZEB1 to macrophages, promoting SIRPα⁺ TAM polarization. Exosomal ZEB1 retains transcriptional activity and activates the STAT3 signaling pathway, reprogramming SIRPα⁺ TAMs. STAT3 inhibition reduces the polarizing effect of exosomal ZEB1, while ZEB1 knockdown increases phagocytosis of CSCC cells by macrophages. These findings suggest that hypoxia-induced ZEB1 strengthens the CD47-SIRPα axis, promoting immune evasion in CSCC. Targeting ZEB1 in combination with CD47-SIRPα checkpoint immunotherapy may improve outcomes for CSCC patients by disinhibiting innate immunity. The study highlights the role of ZEB1 in hypoxic tumor microenvironment and provides new insights into the mechanisms of immune evasion in cervical cancer.