Background: Previous studies have suggested that consuming fruit and vegetable can lower the risk of several cancers, including breast, colorectal, and lung cancers. Aims: The present study aims to investigate the in vitro anticancer effects of Shahani and Asgari grape seed extract (GSE) grown in Malayer City of Iran on HL‑60 cancer. However, to the best of the author’s knowledge, it is the first time in this study that the antiproliferative effect of Shahani and Asgari GSE is compared. Materials and Methods: Shahani and Asgari GSE Was extraction white method of Liquid/liquid extraction with ethyl acetate. Then assessing cytotoxic activities of Shahani and Asgari GSE on the HL‑60 cells was tested using MTT assay. Results: The results show that compared with the control group, seed extract of both Shahani and Asgari at the various concentrations (25, 50, 100, and 200 μg/ml) had a significantly inhibitory effect on HL‑60 cell proliferation that was dose dependent. However, Shahani GSE at different concentrations (50, 100, and 200 μg/ml) indicated a significantly higher inhibitory effect compared to Asgari GSE. In addition, GSE can induce cell cycle arrest at G0/G1 cells. Furthermore, GSE of Asgari and Shahani remarkably increased the induction of HL‑60 cell apoptosis depending on its dose. However, at the concentration of 200 μg/ml, GSE induced cell necrosis rather than apoptosis. Conclusion: Seed extract of both Shahani and Asgari at the various concentrations had a significantly inhibitory effect on HL‑60 cell proliferation that was dose dependent