A 21-year-old Chinese man who took an overdose of acetaminophen was hospitalized. His medical history was significant for glucose-6-phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination was unremarkable and laboratory results were within normal limits. During his hospitalization, the patient experienced a decrease in hemoglobin concentration of almost 4 g/dl and an increase in unconjugated bilirubin consistent with the development of hemolysis. Acetaminophen was the most likely cause of the hemolysis. Clinicians must be aware of this potential complication after acetaminophen overdose in G6PD-deficient patients.