Acute interstitial nephritis is an important cause of acute kidney injury and most often induced by drug therapy. Entecavir is a potent antiviral agent approved for chronic hepatitis B. The antiviral therapy in chronic hepatitis B management is important because it reduces viral replication and liver injury, prevents development of complications, such as liver cirrhosis and hepatocellular carcinoma, and thus improves patient’s survival. The advantage of entecavir is its safety profile, particularly in patients with renal dysfunction. Although doses of entecavir are needed to be adjusted for patients with renal dysfunction, there has been no known renal toxicity of the drug itself. Here we report a patient with chronic hepatitis B and normal renal function who developed acute kidney injury due to tubulointerstitial nephritis after 10 months of entecavir therapy. Renal biopsy showed not only acute changes of interstitial nephritis such as marked cortical infiltration with lymphoplasma cells and neutrophils, mesangial matrix expansion, eosinophilic granular casts and degenerative epithelial cells within tubular lumen but also chronic changes, minimal tubular atrophy and interstitial fibrosis. After immunosuppressant therapy with steroids and mycofenolate mofetil, the patient’s renal function improved.