INTRODUCTION: Melanoma often metastasizes to the liver, leading to significant morbidity and mortality. Liver injury can also occur due to hepatitis caused by immunotherapy used in the treatment of melanoma. CASE PRESENTATION: This case report presents a 38-year-old male diagnosed with advanced melanoma who experienced acute liver failure (ALF) initially thought to be a side effect of immunotherapy. Despite following aggressive supportive care as per the latest guidelines, the patient's condition deteriorated rapidly. It was discovered that the patient had liver metastases. As the tumor had a positive BRAF mutation, we opted for invasive treatment with therapeutic plasma exchange to restore liver function and create the conditions for initiating treatment with BRAF/MEK inhibitors. After the use of a liver support device, the liver function was resolved, and a BRAF/MEK inhibitor was introduced. After 2 months of targeted therapy, a favorable effect and good melanoma control are observed. CONCLUSION: The report underscores the complexity of managing melanoma with liver metastasis and the urgent need for advancements in treatment modalities ALF in oncology patients. We suggest that invasive treatment methods, such as liver support system devices, should be considered in well-selected oncology patients, even in advanced stages of disease.