Introduction: Short peptides have acquired increasing interest as promising therapeutics, particularly as anti-cancer alternatives during the recent years. They have been reported to demonstrate incredible anti-cancer potentials through targeting signalling transduction pathways, as well as modulation of cell cycle, tumour suppressor proteins and transcription factors. Peptides are primarily of interest due to its rapid kinetics, high potency and low biocompatibility issue. In search of novel anticancer leads, the main objective of this study is to evaluate the in-vitro antiproliferative properties of hybridized peptides against human hepatocellular carcinoma (HepG2) cells. Methods: Two series of hybridized peptides, ND and DN analogues were designed based on two parent peptides, NDC1 and NDC2, through fragments hybridization approach. Modification of amino acid residues at specific positions of NDC1 and NDC2 was done at the C-terminal. Then, MTT assay was performed to examine the antiproliferative ranging from 2-256µg/mL for 24 hours. Results: The parent peptide, NDC1 showed an IC50 value of 87±3.786 µg/mL at 24 hours while NDC2 did not display antiproliferative activity against HepG2 cells. ND1-4 showed higher toxicity against Vero cells compared to HepG2 cells while ND5 did not exhibit antiproliferative activities against both cell lines. In contrary, DN1 and DN4 was found to exhibit antiproliferative activity against HepG2 cells, with IC50 values 170±60.883µg/mL and 170±60.883µg/mL, respectively. Meanwhile, both these hybridized peptides showed minimal toxicity against Vero with IC50 values >256µg/mL. In contrast, DN2, DN3 and DN5 showed minimal antiproliferative activity against HepG2 with IC50 values >256µg/mL. Conclusion: Among the ND and DN hybridized peptides, two hybridized peptides, DN1 and DN5, showed potential anti-proliferative activities against HepG2 with minimal toxicity against Vero. Nevertheless, their activity has been diminished as compared to NDC1 and hence, can be further improved.