The extracts of the medicinal plants Achillea santolina and Raphanus sativus have been reported to show anti-cancer effects in vitro. However, the cellular and molecular mechanism of these effects are not clear yet. To compare the apoptotic effects of these plant extracts on different cancer cell lines in vitro. The phenolic, flavonoids and antioxidant activity were determined in the crude extracts. Then, Caco2 (colon adenocarcinoma), HepG2 (hepatic carcinoma), MCF7 (breast cancer) and the normal WISH (amniotic cell line) were treated in vitro with different concentrations of crude extracts for 72 hours. The half maximal inhibitory concentration (IC₅₀) were detected by MTT assay, while cell cycle and apoptosis were assessed by flow cytometry. The methanolic extract of R. sativus seeds (cultivar: Balady) showed higher phenolic content (791.98 mg/d.wt) and higher antioxidant activity (93%) than those of the ethanolic extract of A. santolina (340.23 mg/d.wt) and (72.72%), respectively. R. sativus methanolic extract showed lower flavonoids contents (1.025 mg/g d.wt) than A. santolina ethanolic extract (24.66 mg/g d.wt). Treatment of Caco2, HepG2, MCF7 and WISH cell lines with A. santolina extract showed IC₅₀ of 17.67 µg/ml, 15.12 µg/ml, 42.19 µg/ml and 50.99 µg/ml, respectively. While treatment of the same cell line with R. sativus showed IC₅₀ of 40.77 µg/ml, 27.42 µg/ml, 54.16 µg/ml and 86.37 µg/ml respectively. A. santolina and R. sativus extracts induced similar cell cycle arrest in Caco2 at G1 phase by 42.4%. This study indicates that A. santolina has a potent anticancer activity against the selected cancer cell lines.