【Abstract】Objective To investigate the therapeutic effects of Isaria felina originated from cordyceps sinensis combined with cyclophosphamide in hepatoma H22 tumor-bearing mice. Methods The model of H22 tumor-bearing mice was established and twenty-five Kunming mice were randomly divided into one blank control（NC）and four H22 tumor-bearing groups including tumor model control（MC）, positive control（CTX）, Isaria felina group（IF）and combined administration group（IF + CTX）. The mice in the blank control group and the model control group received distilled water by oral gavage, the mice in the positive control group were intra-abdominally injected with CTX olution（25 mg/kg body weight every day）, the mice in the IF group were orally administered Isaria felina（dispersed in distilled water） at 400 mg/kg body weight, and mice in the combined administration group were administerd the above two medications per day. The adminisation cycle was 10 d. At the end of the experiment, the mean tumor volume and weight, tumor inhibition rate, q value and immune organ index were calculated, and the levels of blood routine and cytokines were determined. The pathomorphological changes of tumor tissues were observed by HE staining. Results the tumor volume and mass of mice in each treatment group were significantly lower than those in MC group（P ＜ 0.05）. The tumor inhibition rates of CTX, IF and IF + CTX groups were 49.3%, 34.2% and 72.8%, respectively and the q value was 1.09. The number of WBC, Lymph and PLT in IF + CTX group was significantly higher than that in CTX group（P ＜ 0.05）. The spleen index of MC group was significantly higher than that of NC group, and the spleen index of IF + CTX group was significantly lower than that of MC group（P ＜ 0.05）. The level of serum IFN- γ in MC group was significantly lower than that in NC group, while the levels of IFN- γ in IF and IF + CTX groups were significantly higher than that in MC group and CTX group（P ＜ 0.05）. Pathologically，the tumor cells in the MC group grew well, numerous and closely arranged. While in the CTX, IF and IF + CTX groups, tumor cells arranged loosely, focal necrosis and nuclear pyknosis of necrotic cells could be seen in many places. Conclusion The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice, which can reduce immunosuppression and myelosup-pression caused by CTX, and have immunomodulatory function. 【Key words】 Isaria felina; H22 tumor-bearing mice; combined administration; immunomodulation