Background Hepatocellular carcinoma (HCC) is one of the most dangerous cancers in all the world. This study focused on prevention and therapy of hepatocellular carcinoma (HCC) using Moringa oleifera extract combined with vitamin C and selenium in a nanoplatform (MO/asc.-Se-NPs). Results Full characterization of MO/asc.-Se-NPs was performed by using different analytical techniques (TEM, DLS, zeta-sizer), and its antioxidant capacity was measured by DPPH assay. Biodistribution study was performed with the aid of radiolabeling technique using technetium-99m in normal albino mice. HCC was induced in Wister albino rats to evaluate the efficiency of MO/asc.-Se-NPs in the treatment of HCC. The biomarker analysis (ALT, AST and ALB) shows improvement in its values in prevention and treated groups by using MO/asc.-Se NP. The levels of inflammatory marker interleukin 6 (IL6 tissue homogenate) was improved by decreasing its values in these two groups also. Histology section of tissue liver showed alleviation in treated and prevention groups. Conclusions In conclusion, MO/asc.-Se-NPs can be used as a potential agent for prevention and treatment of HCC after further preclinical studies.