Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Sorafenib acts as a potential anticancer agent, but it shows less aqueous solubility, so its clinical application is limited. In this present study, we developed Sora-surface decorated iRGD (small cyclic peptide motif (CRGDK/ RGPD/EC)) nanoparticles (labelled Sora-NPs and iRGD@Sora-NPs, respectively) to enhance its aqueous formulation and improve the anticancer activity of Sora. The synthesized Sora-NPs and iRGD@Sora-NPs confirmed by various spectroscopies and electroscopic techniques. Sora-NPs and iRGD@Sora-NPs dramatically suppressed the proliferation of hepatocellular carcinoma cells (BEL-7402 and Huh-7) and showed low toxicity in MTT assays. Compared with free Sora and Sora-NPs, iRGD@Sora-NPs significantly induces the apoptosis in hepatocellular carcinoma cells. The morphological changes were evaluated via various biochemical staining techniques (AO-EB and nuclear staining). Further, the apoptosis mode of hepatocellular carcinoma cell death was confirmed via flow cytometry analysis. Furthermore, the Sora-NPs and iRGD@Sora-NPs promoted apoptotic manner of cell death by G2/M phase arrest. In this present study explained that iRGD@Sora-NPs as a safe and hopeful strategy for chemotherapeutics of hepatocellular carcinoma therapy and deserve further clinical evaluations.