INTRODUCTION: Clozapine can cause major adverse effects, including rare but serious drug-induced liver injury. Understanding how clozapine causes liver injury is crucial for prompt diagnosis and effective management. CASE PRESENTATION: We presented a case of a 42-year-old man with bipolar disorder who presented to our emergency department with a complaint of fatigue, nausea, vomiting, and pain in the upper right abdomen for 1 week. The patient was commenced with clozapine 1 month prior. He appeared jaundiced with a slightly swollen abdomen. Blood tests revealed highly elevated liver enzymes (AST 1679 U/L, ALT 1752 U/L) and bilirubin levels (total bilirubin 8.5 mg/dL, direct bilirubin 3.02 mg/dL). Tests for viral hepatitis and autoimmune diseases were negative. Suspecting clozapine-induced liver injury, we stopped the medication and provided supportive care. DISCUSSION: Clozapine-induced liver injury likely occurs through a variety of pathophysiological pathways that include its metabolism by cytochrome P450 enzymes. Recognizing symptoms like jaundice and abdominal pain early is crucial for diagnosis. Our case reflects similar cases in literature, highlighting the variability in how this condition presents and the importance of prompt intervention to prevent severe consequences. Treatment involves stopping clozapine, supportive care, and closely monitoring the patient's recovery. CONCLUSION: Physicians who prescribe clozapine should make sure that liver function is closely monitored, especially in the initial few months of the medication, and stop it if liver function become more than 3 times of upper limit of normal and patient developed signs and symptoms of liver injury.