Introduction: Traditional treatment of cancer by using chemotherapy not only kills cancer cells but also, normal cells and failed in preventing the spread of the tumor. Chalcone have several biological activities, such as antioxidant, antibacterial, antifungal, anti-inflammatory, and anti-tumor. Aim: To compare the antitumor effects of chalcones in Ehrlich ascetic carcinoma (EAC) bearing mice. Materials and Method: Female Swiss albino mice were randomly divided into 6 groups as the following; Group 1 were served as a negative control, group 2 were inoculated with 2.5×10⁵ (EAC) cells, group 3 were inoculated with 2.5×10⁵ EAC cells and then treated with cisplatin (2 mg/kg), group 4 were inoculated with 2.5×10⁵ EAC cells and then treated with chalcone 1 (0.3 ml gm/L), group 5 were inoculated with 2.5×10⁵ EAC cells and then treated with chalcone II (0.3 ml gm/L). After 7 days, all groups of mice were sacrificed to measure the number and cell cycle of tumor cells as well as the number and activation of CD8⁺ T cells. Results: Treatment of tumor-bearing mice with chalcone I, but not chalcone II induced decreases in the total number of live cells when compared to control tumor-bearing mice, coinciding with significant increases in G0, G1, S and G2 phases of EAC cells which were comparable to the effects of cisplatin. As compared to control tumor-bearing mice, tumor cells harvested from mice treated with chalcone I showed significant increases in the numbers of activated CD8⁺ T cells. Conclusion: Chalcone I possesses anti-tumor effects by inducing tumor cells arrest and activation of T cells.