Hand, foot, and mouth disease (HFMD) is a common viral disease in children. However, adult cases are less frequently seen. We report a family cluster of HFMD involving two children and their father, a patient with history of metabolic dysfunction-associated steatohepatitis proven by liver biopsy. The index case was a 6-year-old girl who developed fever, oral ulcers and blisters, and palm and sole rashes. The infectious cascade turned to her 1-year-old brother with similar symptoms. The father subsequently developed severe adult-onset HFMD characterized by hemorrhagic blisters on both hands and feet, painful oral ulcers, high fever, sore throat, drowsiness, extreme fatigue, shortness of breaths, and elevated liver enzymes. This case highlights the potential for atypical and severe HFMD presentations in adults.