Radiotherapy is currently applied in the treatment of human cancers. We studied whether genistein would enhance the radiosensitivity and explored its precise molecular mechanism in cervical cancer cells. After co-treatment with genistein and irradiation, the viability, cell cycle analysis, and apoptosis signaling cascades were elucidated in CaSki cells. The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone. Treatment with only ${gamma}$-irradiation led to cell cycle arrest at the $G_1$ phase. On the other hand, co-treatment with genistein and ${gamma}$-irradiation caused a decrease in the $G_1$ phase and a concomitant increase up to 56% in the number of $G_2$ phase. In addition, co-treatment increased the expression of p53 and p21, and Cdc2-tyr-15-p, supporting the occurrence of $G_2/M$ arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, down regulation of Bcl-2, and activation of caspase-3 and -8 in the treatment of genistein and irradiation. Apparently, co-treatment downregulated the transcripts of E6*I, E6*II, and E7. Genistein also stimulated irradiation-induced intracellular reactive oxygene, species (ROS) production, and co-treatment-induced apoptosis was inhibited by the antioxidant N-acetylcysteine, suggesting that apoptosis has occurred through the increase in ROS by genistein and ${gamma}$-irradiation in cervical cancer cells. Gamma-irradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and ${gamma}$-irradiation almost completely prevented irradiation-induced COX-2 expression and $PGE_2$ production. Co-treatment with genistein and ${gamma}$-irradiation inhibited proliferation through $G_2/M$ arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.