Dimethylhydrazine (DMH) is very hazardous to the body's organs, especially the liver. 5-fluorouracil (5-FU) is used to treat breast, brain, liver, and colorectal tumours. The effect of 5-fluorouracil nanogel (5-FUNG) in improving the toxicity effect of 1,2-dimethylhydrazine (DMH) on liver was evaluated. Forty rats were separated into 4 groups. Group Ι: (control). Group Π: injected with DMH once a week for eight weeks. Group III: rats administrated DMH then treated with 5-FU 3 times weekly for a month. Group IV: rats administrated DMH then treated with 5-FUNG 3 times weekly by IP injection for a month. Blood samples and liver specimens were taken for determination of some biochemical and molecular biomarkers. DMH induced liver injury by increasing the liver function enzymes and the hepatic inflammatory mediator (IL-1β) compared to control. Additionally, DMH increase the hepatic oxidative stress by increasing MDA level, and decrease in SOD and GSH levels when compared to control group. Group treated with 5 FUNG showing a potent effect than 5-FU in decreasing the levels of ALT and AST and the inflammatory marker IL-1β with increasing in GSH and SOD levels and decreasing in MDA level when compared with the DMH group.