Background Nivolumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death-1. Nowadays, immune checkpoint inhibitors such as nivolumab are used in the treatment of many different types of cancer. Treatment responses of these agents may be different from standard chemotherapy, and hyperprogression is a new entity that occurs with immune checkpoint inhibitors. We present a case of hyperprogressive disease precipitated by anti-programmed cell death-1 immunotherapy. Case Report A 25-year-old woman was treated with ipilimumab, dabrafenib plus trametinib, and nivolumab, respectively, for stage IV melanoma. Palliative whole brain radiotherapy was completed due to brain metastases before the administration of nivolumab. After the fourth cycle of nivolumab, the patient's general condition deteriorated and control positron emission tomography/computed tomography confirmed hyperprogression. Also, brain magnetic resonance imaging indicated the hyperprogression of the metastatic lesions. Management and Outcome After brain magnetic resonance imaging and positron emission tomography/computed tomography showed the hyperprogressive disease, nivolumab was discontinued. Cisplatin and dacarbazine were initiated for melanoma. Discussion Anti-programmed cell death-1 immunotherapy is effective in cancers. These agents can precipitate hyperprogressive disease. As the use of anti-programmed cell death-1 agents is expected to rise, physicians should be educated about the potential possibility of hyperprogression during the immunotherapy.