BACKGROUNDSacha inchi is known for its high protein content and medicinal properties. Bioactive peptides have been reported to have therapeutic potential in various human diseases. However, there is a lack of research evaluating the pharmacological value of peptides derived from Sacha inchi. Therefore, this study aimed to investigate the anti‐hepatoma effect of Sacha inchi peptides (SPs) and their underlying mechanism.RESULTSThe study found that treatment with SPs significantly reduced the proliferation of HepG2 cells by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. SPs also induced HepG2 cell apoptosis by increasing the levels of proteins such as Bax, Caspase‐3 and P53. The study identified nine novel peptides in SPs, of which LLEPDVR, ALVEKAKAS and TGDGSLRPY exhibited higher cell proliferative inhibition rates compared to other peptides.CONCLUSIONThe findings of this study suggest that Sacha inchi peptides have potential pharmacological effects in the treatment of liver cancer. SPs effectively suppress the cell cycle and facilitate cell apoptosis, indicating their anti‐hepatoma effect. The novel peptides identified in SPs may have therapeutic value for liver cancer treatment. © 2023 Society of Chemical Industry.