Cancer is one of the vital causes of morbidity and mortality worldwide and recognized as the second most leading cause of death. Considering the side effects and high cost of synthetic anticancer drugs, plant might act as a source of novel anticancer agents with better host safety. In this investigation, Moringa oleifera leaves methanolic extract (MOLME) was subjected to evaluate its anti-proliferative effect with molecular mechanism in Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. MOLME inhibited EAC cell growth approximately 64% at the dose of 200mg/kg body weight. DAPI stained cells had shown nuclear condensation and fragmentation in treated cells. Up-regulation of pro-apoptotic gene, Bax and tumor suppressor gene, p53; and down-regulation of anti-apoptotic gene Bcl-2 confirm the induction of EAC cells followed by MOLME treatment. Moreover, MOLME inhibited NF-ĸB activity and enhanced ROS generation. Results suggest that the anticancer effect of MOLME is associated with the induction of apoptosis through activation of p53 and reciprocal expression of Bax and Bcl-2. The apoptosis might be triggered by the inactivation of NF-ĸB and generation of ROS. GC-MS analysis revealed that MOLME contains several bioactive compounds, thus it is assumed that the anticancer properties could be attributed by the active leads and could be potential resource of chemotherapeutics.