Hemophagocytic lymphohistiocytosis (HLH) is a highly lethal disease characterized by fever, cytopenia, splenomegaly, and hemophagocytosis. Whereas infectious diseases, malignant tumors, and autoimmune diseases are often triggers for HLH, reports of HLH associated with vaccination are limited. In this report, we describe a case of HLH in a 12-year-old female patient after simultaneous administration of the bivalent messenger RNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine and quadrivalent inactivated influenza vaccine. The patient presented to our hospital with fever on the day after vaccination. Considering the splenomegaly, cytopenia, hemophagocytosis in the bone marrow, and high ferritin level, HLH was diagnosed 12 days after vaccination. Various tests ruled out any infectious disease, malignant tumor, or autoimmune disease. The patient was treated only with 2 mg/kg/day of oral prednisolone, fever improved 13 days after vaccination, and blood test findings rapidly improved. Although HLH after SARS-CoV-2 vaccination or concomitant administration with influenza vaccination is still rare, we emphasize the importance of early HLH diagnosis when persistent fever is observed following vaccination.