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Immunotherapy is now a mainstay in cancer treatments. Programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) therapies have opened up a new venue of advanced cancer immunotherapy. However, hyperprogressive disease (HPD) induced by PD-1/PD-L1 inhibitors caused a significant decrease in the overall survival (OS) of the patients, which compromise the efficacy of PD-1/PD-L1 inhibitors. Therefore, HPD has become an urgent issue to be addressed in the clinical uses of PD-1/PD-L1 inhibitors. The mechanisms of HPD remain unclear, and possible predictive factors of HPD are not well understood. In this review, we summarized the potential mechanisms of HPD and coping strategies that can effectively reduce the occurrence and development of HPD.