Drug-induced liver injury (DILI) is difficult to diagnose as it presents with a wide variety of clinical manifestations and there is no established specific biomarker. However, clinicians require expertise in diagnosing DILI as it can lead to critical illness, is relatively common, and can be caused by a variety of drugs, herbal medicines, and supplements. A 67-year-old male was admitted to the hospital with a fever, jaundice, and fatigue. Abdominal ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography revealed no morphological abnormalities in the hepatobiliary system. On the third day of hospitalization, the liver damage and acute kidney injury progressed, and the patient was transferred to our intensive care unit. To further investigate the cause of multiple organ damage, the patient underwent repeated history taking and additional laboratory testing. In addition to the common causes of hepatic and renal damage, we also tested for rickettsiosis and leptospirosis, as the patient reported partaking regularly in outdoor leisure activities. On day seven of hospitalization, the patient recalled taking over-the-counter herbal flu medications approximately five days prior to admission; therefore, we suspected DILI and performed a drug-induced lymphocyte stimulation test (DLST). The DLST was positive for one drug. As other causes had been ruled out, the patient was diagnosed with severe DILI. The clinical course of the patient was observed with the patient's laboratory data and fever improving spontaneously. This case taught us several important lessons for the investigation of liver injury. Firstly, even with over-the-counter drugs, liver injury can be severe. Secondly, while the DLST is available for investigating DILI, false positives, especially for medicinal herbs, should be noted, and it is necessary to adequately rule out other diseases. Finally, when the cause of liver injury is unclear, patient history taking should be repeated carefully.