Context Cisplastin (CDDP) is a chemotherapeutic drug frequently used to manage a variety of cancers. However, its use is associated with hepatorenal toxicity resulting from elevated reactive oxygen species production. Objective Herein, the hepatorenal protective effect of tert-butylhydroquinone (tBHQ) in cisplatin (CDDP)-treated rats was examined. Methods Wistar male rats randomly divided into four groups: normal control, tBHQ, CDDP and tBHQ + CDDP received 50 mg/kg b.w./day of tBHQ orally for 14 days while 7 mg/kg b.w of CDDP was administered intraperitoneally on Day 8. Results CDDP increased serum biomarkers of hepatic (AST, ALP, ALT, GGT) and renal (creatinine, urea, uric acid, kidney injury molecule 1) function. The levels of nuclear factor erythroid-2-related factor 2 protein and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities were decreased in liver and kidney. Also, CDDP increased hepatic and renal levels of NF-κB, TNFα, Bax and caspase-3 proteins and decreased hepatorenal levels of Bcl-2 protein in the liver and kidney. Pre-treatment with tBHQ prevented these negative effects. Significance Pre-intervention with tBHQ attenuates hepatorenal toxicity of CDDP by dampening oxidative stress, inflammation and apoptosis.