The physical and chemical pressures in the tumor microenvironment (TME) play an important role in tumor development by regulating stromal elements, including immune cells. Hypoxia can induce a cascade of events in tumor initiation and development via immune regulation. As a dangerous factor, hypoxia activates multiple signaling pathways to reshape the immune microenvironment, leading to immunosuppression. Consequently, targeting hypoxia in the TME is a potential strategy to prevent immune escape and inhibit malignant tumor progression. In this review, we summarized the role of hypoxia-induced factors in the tumor immune escape process and provide a novel pathway to restrain tumor progression and development.