Cisplatin (CP) and/ or radiation exposures cause oxidative stress, which induced liver toxicity. The present study was undertaken to explore if fish oil (FO) and /or selenium nano particles (SeNPs) can minimize CP-induced hepatotoxicity and other side effects. Rats were either treated with SeNPs (0.5 mg/kg) and /or FO (2 mg/Kg) for 12 days before treatment with CP (10 mg/Kg) and/ or exposure to γ-rays (0.7Gy).The results of the present study revealed that rats treated with CP and /or γ-radiation showed an increase in the level of IL6, renin and the expression of angiotensinogen , xanthine oxidase (XO) and NF-κB protein along with a decrease in (Nrf2) protein expression as well as, the activity of antioxidant enzymes. Fish oil and /or selenium nanoparticles (SeNPs) treatment prior to CP and/ or radiation exposure normalized these parameters. Our findings suggest that FO together with SeNPs could be used as protective supplements against toxicity associated with ionizing radiation and CP due to its antioxidant, anti-inflammatory and anti-apoptotic properties.