Background: Numerous reports on the side effects of anti-cancer drugs have encouraged scientists to search for alternative anti-cancer agents with higher efficacy and fewer side effects. The current investigation was intended to study the anti-tumor efficacy of Terfezia claveryi Chatin methanolic extract (TCME) on mice with Ehrlich solid tumors (EST). Materials and Methods: EST mice received TCME at doses of 50 and 100 mg/kg orally once a day for two weeks. To study the anti-tumor effects, the rate of tumor growth, weight of the body, the serum level of some tumor markers, enzymes related to liver and kidney function, oxidant and antioxidant enzymes, tumor necrosis factor alpha (TNF-α) level, and some genes related to apoptosis were investigated. Results: The results revealed that the growth rate of the tumor, tumor markers, oxidative markers, enzymes related to liver and kidney function, level of TNF-α, and Bcl-2 gene expression were considerably declined in the EST mice receiving the TCME, whereas the enzyme levels related to antioxidant activity as well as Bax and caspase-3 gene expression were considerably elevated (P < 0.001). Conclusion: We found that T. claveryi methanolic extract has relevant anti-tumor efficacy on mice with EST and might be considered as a substitute anti-cancer compound; however, more studies especially in vulnerable humans are mandatory to approve these outcomes.