|Cancer as a threat to human life disease is considered by the disturbance of the normal cell cycle, which results in the spontaneous growth of cell growth, the lack of differentiation, and consequently malignant growths. Nowadays, various synthetic agents are applied for cancer therapy; nevertheless, the reports confirmed that these chemical agents are related to various adverse complications. This experimental study was designed to assess the anti-tumor activities of zinc nanoparticles (ZnNP) green synthesized by the Astragalus maximus against the Ehrlich solid tumors (EST) in mice. To induce the EST model, 0.2 ml of cell suspension was intramuscularly injected into the right thigh of the mice. Five-day post-injection, the mice were allocated into five groups (containing 8 mice/each group) including EST mice treated with normal saline, EST mice orally treated ZnNP 10 mg/kg/day, EST mice orally treated ZnNP 25 mg/kg/day, and EST mice orally treated ZnNP 50 mg/kg/day for 14 days. Then, the volume of the tumor, tumor growth inhibition, body weight, the tumor markers, oxidant/antioxidant markers, and tumor necrosis factor-alpha level (TNF-α), were assessed in tested mice. Our results showed that after the treatment of EST mice with CYC and ZnNPs at 10, 25, and 50 mg/kg, the volume of tumor and serum amount of tumor markers of AFP and CEA were significantly reduced (p<0.001). We found that ZnNPs at 10, 25, and 50 mg/kg markedly declined the oxidative markers and increased the level of antioxidant enzyme of SOD and GPx in comparison with the control group received normal saline (p<0.001). To conclude, we reported the unveiling of the anti-tumor activity of ZnNPs green synthesized by A. maximus extract mainly at the doses 50 mg/kg against Ehrlich solid tumors (EST) in mice; however, further supplementary studies are required to clear all anti-tumor aspects of these nanoparticles.