Nearly all medications carry the risk of drug-induced liver injury (DILI). Idiosyncratic reactions are rare and poorly predictable, and the mechanisms are not always well understood. Pirfenidone is an oral antifibrotic drug used to treat idiopathic pulmonary fibrosis. While elevation of liver enzymes is a common adverse reaction during therapy, it rarely leads to discontinuation or reduction of the drug. Although isolated cases of liver damage or liver failure have been reported, they are infrequent. This report presents the case of a 70-year-old woman with known idiopathic pulmonary fibrosis, depression, hypothyroidism, and hypercholesterolemia who presented at our emergency department with jaundice, anorexia, and asthenia. The patient's medication regimen included lamotrigine, simvastatin, levothyroxine, and pirfenidone, which had been introduced 6 months prior. Laboratory testing revealed elevated liver enzyme levels consistent with acute hepatocellular hepatitis. Following a medical workup, which included anamnesis, laboratory testing, iconographic investigations, and liver biopsy, we concluded that the patient had suffered from pirfenidone-induced liver injury. Pirfenidone was withdrawn, and liver tests gradually improved. The purpose of this clinical case report is to highlight this rare adverse reaction and to make clinicians aware of its assessment and management. In 2018, only one other case of severe liver failure leading to the death of the patient was reported. Early detection of potential DILI during the workup is crucial to discontinue the suspected medication promptly. Any drug-induced hepatitis must be reported for registration. A case report of toxic hepatitis induced by drug (pirfenidone) in a patient with idiopathic pulmonary fibrosis center dot Drug-induced liver injury (DILI) is a type of hepatitis caused by medication, drugs, or even herbal and dietary supplements. center dot There are two types of DILI reactions: intrinsic and idiosyncratic. circle The intrinsic reaction, such as acute hepatotoxicity due to acetaminophen overdose, is easily predictable and well-known. circle The idiosyncratic reaction is more complex, unpredictable, and not well-understood. Therefore, diagnosing an idiosyncratic reaction can be challenging. center dot Pirfenidone is an immunosuppressive drug used to treat idiopathic pulmonary fibrosis by inhibiting collagen formation through anti-fibrotic and anti-inflammatory mechanisms. center dot Several adverse reactions of pirfenidone are well described, including temporary elevation of liver enzymes during treatment. This adverse reaction is mostly asymptomatic and resolves spontaneously with or without dose adjustment. center dot However, few cases of severe DILI due to pirfenidone have been reported, which may lead to liver dysfunction. center dot This paper reports on a rare idiosyncratic reaction related to pirfenidone that resulted in hepatic adverse reactions.