Hepatocellular carcinoma (HCC) is the third deadliest and fifth most common cancer worldwide. Many drugs that have the potential to treat cancers have had limited success due to their lack of efficient and safe delivery mechanisms that allow the drug molecules to cross cell membranes. Electrical pulses-mediated drug delivery, known as electroporation, is gaining attention as a possible approach to enhance uptake of chemotherapy. The present work studied the effect of silver nanoparticles encapsulated by doxorubicin drug in the treatment of hepatocellular carcinoma. The study was conducted on 40 albino mice weighting 20-25 g of 8-10 weeks of age, and were divided into two major groups. Group A:10 mice were used as a control , group B: 40 mice have induced HCC by DABE this group were subdivided into three subgroups; sub groupB1 10 mice which were not received any treatment, and were kept at room environment and, sub group B2: 10 mice were injected i.p with a dose of 50 mg/kg body weight of doxorubicin only every day for 21days, sub group B3 :10 mice were injected i.p. with a dose of 50 mg/kg body weight of doxorubicin encapsulated by the silver nanoparticles every day for 21days.Parts of liver tissue and blood samples were collected from all from mice of each group for histopathological examination; the nanocapsules were of the size range 200 ± 20 nm and loaded with the positively charged anticancer drug doxorubicin with an efficiency of 89%. The loading of the drug into the capsule occurs by virtue of the pH-responsive property of the capsule wall, which is determined by the pKa of the polyelectrolytes. As the pH is varied, about 64% of the drug is released in acidic pH while 77% is released in neutral pH. Molecular detection of Alpha-fetoprotein (AFP) and Glypican-3 (gly3) mRNAs by RT-PCR before and after treatment by silver nanoparticles encapsulated doxorubicin drug were studied in mice with HCC. Silver nanoparticles encapsulated doxorubicin drug showed effective results for treatment of HCC compared to results obtained with doxorubicin drug resulting in reduced tumor growth, and induction of apoptosis in the treated cells by enhancing of delivering chemotherapy and anticancer drugs with enhanced efficacy and fewer adverse effects.