Venlafaxine is among the most widely prescribed antidepressants. It is extensively metabolized to O-desmethylvenlafaxine via cytochrome P450 (CYP) 2D6. We report a case of acute toxic hepatitis resulting from venlafaxine in a 54-year-old woman with pain disorder. During venlafaxine treatment, laboratory tests revealed elevated liver enzymes with a maximum of 169 IU/L for aspartate transaminase (AST) and 166 IU/L for alanine transaminase (ALT). AST and ALT levels returned to normal after 6 days of discontinuation of venlafaxine. The patient was finally diagnosed with acute toxic hepatitis through liver biopsy. This case indicates the importance that clinicians should be aware of the hepatotoxicity of venlafaxine in practice.