Background: hepatocellular carcinoma (HCC) is the most common type of primary liver cancers with high incidence and mortality rates. The major risk factor for HCC is cirrhosis, which occurs usually due to HBV and HCV infection. Exosomes thought that have a major role on the promotion and spread of HCC, which can be uased as therapeutic and diagnostic marker. Objectives: we aimed to use evaluate their role in HCC assessment and their use as potential selected diagnostic biomarkers, and to characterize the efficacy of Hesperidin on modulating exosomal production and exosomal non-coding RNA related HCC expression using animal models. Materials and Methods: the study included 30 Rats devised to 5 groups 6 on each, controle and DiethyleNitros amine (DEN) and Acetamidofluorene (2-AAF) to iduce HCC group and Hispiridine treated groups with three different dosos 50 mg, 100 mg and 200 mg respectively for three groups. infants with neonatal cholestasis in three groups. Results: improvement of all of them, regarding liver histopathology wich the HCC focus regressed , regarding exosomal abundance in the serumand tissues while the evaluation of exosomal RAB11A-mRNA in rats' samples was performed by real time PCR, then the results were statistically analyzed by the SPSS software. Finally regarding to liver function test which the ALT, bilirubin and AFP reduced in the treated groups. Conclusion: exosomal RAB11A-mRNA as biomarkers for HCC inducedrats and target these exosomal markers using Hesperidin in animal model and hence we can uses as thrapuetic bases in HCC in the future.