Introduction: Liver is a critical organ that detoxifies toxic compounds, metabolizes drugs and excretes waste products. Liver is sensitive to damage, and anticancer therapy. Cytarabine is the main drug used to treat non-Hodgkin lymphoma and acute myeloid leukemia. However, due to its side effects, a new combination is needed to improve treatment outcomes. Tribulus terrestris is a traditional plant that has anticancer activity and many chemical and biologically active substances with anti-inflammatory and antioxidant properties. This study investigated the effect of T. terrestris L. extract against the hepatotoxicity induced by cytarabine in rats. Material and method: A total of 24 adult male rats were divided into 4 groups (n=6), control (saline 1ml/kg), cytarabine (25 mg/kg), T. terrestris (250 mg/kg), and cytarabine + T. terrestris extract. Saline and Cytarabine were administrated intraperitoneally and T. terrestris extract was gavaged every day for four weeks. At the end of the treatments, blood serum samples were used for enzymes and antioxidant measurements, and liver samples were used for histological examination. Results: In the cytarabine group, the level of aspartate aminotransferase, alanine transaminase, and malondialdehyde significantly increased and the levels of antioxidant enzymes significantly decreased compared to the control group. Also, the liver tissue had severe damage. In cytarabine and T. terrestris extract group, the level of antioxidant enzymes increased and malondialdehyde level, liver enzymes, and liver tissue damage decreased compared to the cytarabine group. Conclusion: Our results indicate that T. terrestris with a dose of 250 mg/kg could provide a significant protective effect against cytarabine hepatotoxicity.