A 42-year-old man with lung squamous cell carcinoma [cT2bN3M1b (HEP, PUL, PLE), stage IV B], was given pembrolizumab (200mg every three weeks) as a second-line treatment. Fifteen days after the administration of the third course of pembrolizumab, he presented with grade 1 diarrhea, fever, and abdominal pain. Contrast-enhanced computed tomography showed edema and a thickened rectal wall. The symptoms progressed, and lower gastrointestinal endoscope revealed loss of vascular marking and purulent exudate. As histological and culture tests did not show a specific etiology such as bacterial enterocolitis or clostridium difficile-associated colitis, we concluded it to be pembrolizumab-induced colitis. Prednisolone 70mg was administered, but the disease continued to progress. It was also refractory to anti-TNFα antibodies. Tacrolimus alleviated the fever and abdominal pain and the patient was able to restart oral intake, but the diarrhea continued. Pembrolizumab only rarely causes drug-induced colitis, but when it does occur, it can be serious. This is the first recorded case of severe pembrolizumab-induced anti-TNFαantibody-refractory colitis in Japan.