Abstract: To observe the inhibitory effect of the combination of xiaoaiping injection and octreotide on H22 tumor-bearing mice, to determine the optimal drug concentrations, and to explore their possible mechanisms of action. Methods: To establish a mice H22 subcutaneous tumor model, the experimental animals were randomly divided into the following model groups after tumor formation: the low-, medium-, and high-dose XAP groups, the OCT group, and the low-, medium-, and high-dose XAP with OCT groups. After 14 days, the splenic tissues were collected to measure the spleen index; the transplanted tumors were excised after treatment and weighted to calculate the tumor growth inhibitory rates; the level of cytokine production of Th1 ( IL-2, IFN-γ ) and Th2 ( IL-4, IL-10 ) was detected with the ELISA method; and the expression of apoptosis proteins Bcl-2 and Bax was determined by immunohistochemistry. Results: The growth of the H22 liver cancer cells in the different treatment groups were inhibited by the treatments; the inhibition in the combination groups was better than in the single-agent groups ( P < 0. 05 ). Xiaoaiping + octreotide produced a synergistic effect and the group treated with high-dose xiaoaiping + octreotide exhibited the best inhibition rates. The combination group had an increased spleen index, correcting the imbalance in cytokines and upregulating the expression of the apoptosis-promoting gene Bax, downregulating the expression of the apoptosis-inhibiting gene Bcl-2. The effects of the combination treatment were significantly better than those in the single drug group, namely the octreotide monotherapy and the xiaoaiping monotherapy. Conclusion: High-dose xiaoaiping with octreotide is the best concentration for tumor-inhibition. To some extent, the treatment increased the apoptosis rate of the H22 tumor cells in vivo. It also improved the cellular immunity of the mice bearing the H22 cells.