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Aim The aim of the current study is to investigate the antioxidant and apoptotic potential of Ajwa date flesh (ADF) and Ajwa date pit (ADP) extract on human squamous cell carcinoma cell line (HSC-2). Method ADF and ADP were extracted with a solvent extraction method using hexane, acetone, and ethanol, which were then subjected to antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl (DPPH). HSC-2 cells were then treated with different concentrations of ADF and ADP extract for 24, 48, and 72 hours. MTT assay was performed to assess the antiproliferative effect, and Annexin V-FITC was used for the detection of cellular apoptosis. Results Acetone extracts of ADF and ADP had the highest radical scavenging and antioxidant activities followed by the ethanolic extracts, whereas ADP appeared to have significantly higher antioxidant effects than ADF. MTT assay demonstrated that acetone extracts of ADF and ADP were significantly cytotoxic against HSC-2 cells in a dose- and time-dependent manner. The half inhibitory concentration (IC50) of ADF was found to be 8.69 mg/ml at 24 h, and the maximum cell growth inhibition was observed at 50 mg/ml. The IC50 for the ADP was found to be 0.97 mg/ml at 24 h, and the maximum cell growth inhibition was observed at 5 mg/ml. Statistical analysis of the flow cytometry assay showed that the treatment with ADF and ADP extracts had a significant apoptotic effect which occurred in a dose-dependent manner. HSC-2 cells were seen in the late apoptotic stage with higher doses of ADF and ADP extract. ADP extract demonstrated higher apoptotic activity than ADF extract. In addition, combined treatment of ADF and ADP was also performed on HSC-2 cells which demonstrated higher apoptotic activity when compared to the single extract. Conclusion Ajwa date fruit has a promising cytotoxic effect by inhibiting the growth and proliferation of OSCC cells and inducing cell death by apoptosis.