Programmed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies and have been shown to increase patient survival in several studies. However, these drugs have a toxicity profile that ranges from mild side effects such as dermatitis to life-threatening complications. We present a case of pembrolizumab-induced hemophagocytic lymphohistiocytosis (HLH) in an 80-year-old patient with squamous cell carcinoma (SCC) of presumed cutaneous primary. This patient initially presented with weakness and pancytopenia, thought to be immune-related. She developed progressive anemia, after which further workup revealed concern for HLH. She recovered after a course of steroids, tocilizumab, and etoposide. To our knowledge, this patient’s course is among a few rare cases of immune checkpoint inhibitor (ICI)-mediated HLH. This case highlights the need for early diagnosis and recognition of HLH as a potential toxicity related to ICI therapy.