Objective: At present, many chemotherapy drugs are the products of natural origin or derived from them. Optimum plant derivations specifically deal with the formation of new vessels in tumors without major complication without any toxicity for normal tissues. In this study, anti-angiogenesis activity and anti-tumor of the hydroalcoholic extract of oak was studied. Materials and Methods: After preparation of hydroalcoholic extract of oak, different concentrations of it were assayed on the three-dimensional model of human umbilical endothelial cells. Then, possible angiogenesis inhibition mechanism of the extract (by inhibiting the VEGF factor and matrix metalloproteinase enzymes (MMPs)) was evaluated byusing laboratory techniques such as ELISA and Zymography. Moreover, the antitumor effect of extract on gastric cancer cells was studied by treatment with various doses of hydroalcoholic extract of oak. Results: The results showed that hydroalcoholic oak has significant inhibitory potential on growth and proliferation of gastric tumor cells so as the extract at appropriate concentration could inhibit the proliferation of this cancer cell line (as a solid tumor). Conclusion: Our study showed that hydroalcoholic extract of oak has remarkable anti-angiogenesis and also anti-cancer effects. Therefore, oak plant can be as a suitable candidate for further research as a drug used in pathological states such as angiogenesis-dependent cancers, especially gastric cancer, which today is one of the most common and most deadly cancers in the world, and possibly some chronic diseases.