Introduction: Lung cancer ranks among the foremost causes of mortality associated with cancer. Ensartinib is a highly effective oral anaplastic lymphoma kinase (ALK) inhibitor utilized in the treatment of ALK-positive lung adenocarcinoma. This report presents a case of acute renal failure attributed to the administration of ensartinib. This is the first case report documenting the nephrotoxic effects of ensartinib, specifically manifesting as acute tubulointerstitial nephritis (ATIN) and IgA nephropathy. Case presentation: This report details the case of a 52-year-old man diagnosed with ALKpositive lung adenocarcinoma. The patient was initially treated with crizotinib for a duration exceeding 6 months; however, he was subsequently transitioned to ensartinib due to disease progression characterized by the development of brain metastases. Within 3 months of initiating treatment with ensartinib, the patient experienced acute kidney failure. The renal failure was attributed to ATIN and IgA nephropathy, which were considered manifestations of renal toxicity associated with ensartinib. Conclusion: This case underscores the uncommon adverse effect of ALK-targeting therapy, specifically regarding acute renal failure induced by ensartinib. We recommend conducting a renal biopsy to ascertain the presence of drug-induced nephrotoxicity. An accurate diagnosis and timely intervention can prevent the deterioration of renal function.