Date (Phonix dactylifera) has great interest in biomedical applications. This study was conducted to evaluate the phytochemicals constitute, antioxidants activity, in vitro and in vivo anticancer activity of P. dactylifera seeds extract (PDSE). Phytochemicals analysis (qualitative and quantitative), two different human cancer cell lines and murine Ehrlich ascetic carcinoma (EAC) bearing mice were used. The phytochemical analysis showed that the total phenolics, flavonoids, saponin and anthocyanin contents were 1479, 219, 11600 μg/ml and 212 μg/g, respectively. Total antioxidant capacity, DPPH scavenging percentages were 98 μg/ml, and 84 %, respectively. In vitro inhibition concentration (IC50) of PDSE against breast (MCF-7) and hepatic (HepG-2) cancer cell lines were 25.2 and 40.5 μg/ml, respectively. Treatment with PDSE (100 mg/Kg) decreased the total volume and counts of tumor. Biochemically, PDSE treatment ameliorated the hematological, hepatic, renal and oxidative stress post tumor challenge. Collectively, PDSE have promising natural cancer-fighting phytochemicals.