Cisplatin (CP) is one of the most frequently used chemotherapy agents. The objective of this design was to determine the ameliorative effect of lycopene (LP) and/or N‑acetylcysteine (NAC) in rats with hepatic and renal toxicity induced by CP. Rats were divided randomly into 7 groups (7 rats/ group): control vehicle group (saline only), the LP group (10 mg/kg, orally), the NAC group (150 mg/ kg, orally), the CP group (7.5 mg/kg, IP on day 27), the LP‑CP group, the NAC‑CP group, and the LP‑NAC‑CP group. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (APK), and levels of urea, creatinine, and lipids (cholesterol, triglycerides, and low‑density lipoprotein‑cholesterol) increased after CP injection in the serum. Moreover, CP decreased levels of protein, albumin, and HDL cholesterol. Meanwhile, malondialdehyde significantly increased with a decrease in reduced glutathione, superoxide dismutase, and catalase in the liver and kidney tissues. CP also induced some pathological lesions and increased the expression of caspase‑3 in the liver and kidney tissues. Administration of LP and NAC alone or in combinations ameliorated hepatorenal toxicity and apoptosis induced by CP.