A 50-year-old male patient who had undergone liver transplantation for over 3 years, and received radiotherapy for sternal and thoracic vertebral bone metastases 1 year earlier. He had been on lenvatinib-targeted therapy for over 10 months. Upon admission, he developed marked proteinuria (24-hour urine microalbumin 11,803.18 mg↑↑, 24-hour urine total protein 16,338.5 mg↑↑, and renal biopsy revealed glomerular microangiopathy. After multidisciplinary consultation, the condition was determined to be lenvatinib-associated renal injury, with a Naranjo's Adverse Drug Reaction Probability Scale score of 7, indicating a "probable" causal relationship. Based on the clinical status and current evidence, the clinical pharmacist recommended permanent discontinuation of lenvatinib, and subsequent anti-tumour regimen switched to regorafenib tablets combined with denosumab injection for bone repair therapy. Following the clinical adoption of the recommendations, the patient's renal injury did not recur after adjustment. This patient presented a complex case of recurrent hepatocellular carcinoma post-liver transplantation, with long-term immunosuppressive therapy and over 20 years of hypertension history, developing significant proteinuria with renal damage and nephrotic syndrome, representing a severe adverse event with multiple risk factors. Clinical pharmacists participated in pharmaceutical care, providing individualized recommendations for the differential diagnosis, clinical management, and subsequent treatment transition of lenvatinib-related serious proteinuria and renal injury adverse events, and offering a theoretical basis for the clinical diagnosis and treatment of targeted therapy drug-induced liver injury.

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