Background: Research the antitumor effects of ethanol extracts from Hyptis rhomboidea in H22 tumor-bearing mice. At the fist-stage of the experiments, the research team took MTT method to measure the antitumor activity in vitro, then selected the most inhibitory tumor cell strain as the test object of antitumor activity in vivo, established three models of a solid tumor H22 liver cancer, ascites tumor, and immunodeficiency in male mice. From inflammatory factor, liver toxicity, in vivo antioxidant index to observe antitumor activity of ethanol extracts from H. rhomboidea. Materials and Methods: Hundred and twenty ICR male mice were used to establish three models of a solid tumor H22 liver cancer, ascites tumor, and immunodeficiency in male mice and models group of a solid tumor H22 liver cancer randomly divided into six groupshe normal control group, the model control group, the positive group (cyclophosphamide), the sample treated group (high - 1.300 g/kg, medium - 0.750 g/kg, low - 0.373 g/kg). The animals were sacrificed 15d after oral administration and tumors were taken out for the tumor weights and antitumor rates. Blood in eyeball was collected for the determination of aspartate transaminase, alanine transaminase, malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-2, and tumor necrosis factor (TNF)-α in serum. Sections of tumor issue were prepared, and morphological changes in tumor tissue cells were observed using hematoxylin and eosin staining technique. Results: The results showed that ethanol extracts from H. rhomboidea have a certain inhibitory effect on the digestive tumor cells. In solid tumor model, the inhibitory rate is up to 68.84% of the high dose of treated group from H. rhomboidea, and H. rhomboidea could improve the immune organ index, decrease the concentration of TNF-α and IL-2 in serum. In ascites tumor model, H. rhomboidea could slow down weight gain in mice and prolong the survival time; in immunodeficiency model, H. rhomboidea could improve the serum TNF-α and, IL-2 levels, increase SOD activity, and reduce MDA content, so as to achieve antitumor effect. Conclusions: Ethanol extracts from H. rhomboidea have obvious antitumor activity in vivo and can improve a tumor-burdened mice inflammation factors, improve the survival quality of H22 tumor mice, and enhance immunity and antitumor activity.