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Despite technological advances in cancer treatment, especially in radiotherapy, many efforts are being made in improving cancer cell radio-sensitivity to increase therapeutic ratio and overcome cancer cell radio-resistance. In the present review, we evaluated the anticancer mechanism of Annona muricata L. (AM) leaves extract and its bioactive compounds such as annonaceous acetogenins, annomuricin, annonacin, or curcumin; and further correlated them with the potential of the mechanism to increase or to reduce cancer cells radio-sensitivity based on literature investigation. We see that AM has a promising future potential as a radio-sensitizer agent.