A 70-year-old man was diagnosed with lung adenocarcinoma [cT1cN1M1c (BRA), Stage IVB] and received nivolumab as the second-line treatment. After seven cycles of nivolumab, thrombocytopenia occurred. Since the platelet counts increased and decreased after discontinuation of nivolumab, a bone marrow biopsy was performed. We considered immune thrombocytopenia as a differential diagnosis because of the increase in megakaryocytes; however, we continued to observe the patient due to the normalization of the platelet count. A few days later, he was hospitalized for cerebellar hemorrhage, and laboratory results revealed significant thrombocytopenia and hemolytic anemia. We suspected an immune-related adverse event secondary to nivolumab, and administered systemic glucocorticoids, following which the platelet counts increased immediately. Laboratory results revealed severe deficiency of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity, and the presence of ADAMTS13 inhibitor. The final diagnosis was acquired thrombotic thrombocytopenic purpura (TTP) secondary to nivolumab. Although rare, TTP should be considered as a differential diagnosis of thrombocytopenia after the administration of nivolumab.