OBJECTIVE Medical halophytes plants are potent sources of bioactive secondary metabolite components used against different diseases. Avicenniamarina one of the typical halophytes plant species used in folk medicine to treat smallpox, rheumatism, and ulcer. Despite the richness of A.marina with polyphenolic, flavonoids, terpenoid, and terpene, contents remain poorly investigated against cancer types. Consequently, to explore the function-composition relationship of A.marina hexane leaves crude extract, the current study designed to investigate the cytotoxicity, apoptotic and antiproliferative impacts on the colon (HCT-116), liver (HepG2), and breast (MCF-7) cancer cell lines. METHODS Therefore, the cytotoxicity impact screening carried out by Sulforhodamine-B assay. While, the initiation of the apoptosis evaluated by chromatin condensing, early apoptosis, late apoptosis and the formation and appearance of apoptotic bodies. On the other hand, the flow cytometry used to identify the phase of inhibition where the determined IC50 value used. While, the chemical composition of the hexane extract was detected using liquid chromatography-mass spectrometry/mass spectrometry. RESULTS Revealed that hexane extract showed a weak induction of apoptosis despite the formation of apoptotic bodies and the high cell inhibitory effect on all tested cell lines with IC50 values (23.7 ± 0.7, 44.9 ± 0.93, 79.55 ± 0.57) μg/ml on HCT-116, HepG2, and MCF-7, respectively. Furthermore, it showed the ability to inhibit cell cycle in G0/G1 for HCT-116, S phase for HepG2, and MCF-7. CONCLUSIONS In the light of these results, the current study suggests that A.marina leaves hexane extract may be considered as a candidate for further anticancer drug development investigations.