Reduction of S100A2 level is associated with reduced cervical cancer cell phenotype, evidenced by reduced cell proliferative, invasion, and migration, and that phenotype reduction mediated by S100A2 knockdown antagonizes hypoxia action, suggesting S100A2 could be a crucial hypoxia mediator that drives cervical cancer phenotype and immunotherapy resistance by regulating PD-L1. Here, S100A2 is linked to cervical cancer.