Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPa axis. Hypoxia increases ZEB1 expression in cervical squamous cell carcinoma (CSCC) cells, leading to increased infiltration of tumor-associated macrophages (TAMs). ZEB1 expression is closely correlated with CD47-SIRPa axis activity in CSCC, enabling cancer cells to evade phagocytosis by macrophages and promoting tumor progression. ZEB1 directly activates the transcription of the CD47 gene in hypoxic CSCC cells. Endogenous ZEB1 is enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes, promoting SIRPa+ TAM polarization. Intriguingly, exosomal ZEB1 retains transcriptional activity and reprograms SIRPa+ TAMs via activation of the STAT3 signaling pathway in vitro and in vivo. STAT3 inhibition reduces the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increases the phagocytosis of CSCC cells by macrophages by decreasing CD47 and SIRPa expression. These findings suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPa axis, and targeted therapy of ZEB1 combined with CD47-SIRPa checkpoint immunotherapy may improve outcomes for CSCC patients by disinhibiting innate immunity.Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPa axis. Hypoxia increases ZEB1 expression in cervical squamous cell carcinoma (CSCC) cells, leading to increased infiltration of tumor-associated macrophages (TAMs). ZEB1 expression is closely correlated with CD47-SIRPa axis activity in CSCC, enabling cancer cells to evade phagocytosis by macrophages and promoting tumor progression. ZEB1 directly activates the transcription of the CD47 gene in hypoxic CSCC cells. Endogenous ZEB1 is enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes, promoting SIRPa+ TAM polarization. Intriguingly, exosomal ZEB1 retains transcriptional activity and reprograms SIRPa+ TAMs via activation of the STAT3 signaling pathway in vitro and in vivo. STAT3 inhibition reduces the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increases the phagocytosis of CSCC cells by macrophages by decreasing CD47 and SIRPa expression. These findings suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPa axis, and targeted therapy of ZEB1 combined with CD47-SIRPa checkpoint immunotherapy may improve outcomes for CSCC patients by disinhibiting innate immunity.