Acute necrotizing encephalopathy of childhood (ANEC) is a rare condition of encephalopathy which commonly occurs in healthy children. This case report will discuss the diagnostic approach in a female child, three years old, with neurologic deficits. The diagnostic approach of ANEC consists of clinical manifestation, laboratory examination, cerebrospinal fluid (CSF) analysis, and neuroimaging interpretation. The patient had high liver enzyme, normal CSF analysis with appearances of edema, hemorrhage and necrosis in serial brain magnetic resonance imaging (MRI).