5 Fluorouracil^® (5-FU) is a commonly used anticancer medication that works by preventing the replication of the DNA. While 5-FU's adverse effects are extensively reported, the mechanism underlying 5-FU's hepatotoxic effects remains unclear.The aim of this investigation was to assess the potential antioxidant; anti-inflammatory and hepatoprotective mechanism of sea anemone extract (SE) induced hepatotoxicity.Four groups of animals were randomly assigned as follows: 1) Healthy reference group; 2) Oral administration of SE (50mg/ kg/ day) to healthy rats; 3) Hepatotoxicity model animals, and 4) hepatotoxicity model animals receiving SE.Results showed that SE was able to reduce hepatotoxicity after six weeks of therapy; this was demonstrated by a marked increase in albumin and total protein as well as hepatic GSH, SOD, and CAT values, along with a significant decrease in serum ALAT, ASAT, GGT, ALP, bilirubin, TNF-α, IL-1β, IL-4, IL-6, IL-10, and AFP values. These effects significantly reduced hepatic MDA, NO, and DNA fragmentation. It can be concluded that SE was highly successful in mitigating the oxidative stress caused by hepatotoxicity and shielding the liver from its harmful effects. As such, SE is a promising supplement candidate for shielding the liver from the negative effects of chemotherapy medications.