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In the literature, there is no reported case of liver enzyme elevation related with paliperidone palmitate (PP). In this case, we report a schizophrenic patient who developed liver enzyme elevation after the first dose of PP. The patient was admitted to our in-patient unit and was not on any medication for the last 9 months. For routine medical examination, blood samples for biochemical tests, complete blood count, thyroid function tests, viral hepatitis markers were requested and all of them were within normal limits. She had no family or personal history of liver disease and no history of alcohol or substance abuse. After the administration of intramuscular PP 150 mEq, she complained for nausea. The following day, Aspartate aminotransferase(AST) level was 100 IU/L, alanine aminotransferase (ALT) level was 118 IU/L. After 6 days of the first PP dose, liver enzyme levels decreased to normal limits. On the 8th day of PP injection, the second initiation dose of 100 mg intramuscular PP was administered. After 2 days, the patient had no complaint of nausea, but AST level was 87 IU/L and ALT level was 91 IU/L. In the following 4 days, liver enzyme levels were gradually decreased to normal values. Clinicians should be aware of the possibility that PP can cause hepatotoxicity and this adverse event may be more difficult to deal with long-acting injectable agents like PP.