Abstract: Background and Objective: Atorvastatin (AV) is statin drug that lower peripheral cholesterol production to prevent cardiovascular disease and became of interest in cancer prevention. This study was to articulate the possible inhibitory potential of AV and gamma radiation on STAT-3 and β-catenin signals during cancer evolution. Materials and Methods: Ehrlich ascites carcinoma (EAC) cells (2.5×106 cells/mouse) were inoculated to mice subcutaneously in the right thigh at zero time synergistically with starting AV administration (10 mg kg–1 b.wt.,/day for 21 days). Accordingly, mice were exposed to (4 Gy) of gamma radiation at the 13th days from experiment commence. The statistical analysis of the results was performed by one-way analysis of variance (ANOVA). Results: MTT assessment identified that AV addition to culture of EAC cells in a proper concentrations decreased cell viability in a dose dependent manner: (IC50 = 512 mg L–1: LD50 = 63 mg kg–1). The injection of the AV and the exposure to gamma radiation markedly decreased the tumor volume when compared to E mice. Further, the concentrations of lipid peroxides (MDA) and Glutathione (GSH) as well as the activities of glutathione peroxidase (GPX) and glutathione transferase (GST) were significantly ameliorated, in addition to decreased in the levels of β-catenin and STAT-3 mRNA expression and the concentration of p-STAT-3. Also, the expression of p53 mRNA is significantly improved when AV administrated. Conclusion: Credibly, the AV blockade of STAT-3 convenient activation might turned out the β-catenin expression, leading to stopping tumor progression. Exposure of mice bearing Ehrlich solid tumor to gamma radiation seemed to have a capability to proceed the action of AV. Actually, the overall results support the antitumor effect of AV which could be potentiated by radiotherapy.