Abstract: Objective To investigate the effect of aplysin on tumor invasion and immunomodulation in mice with hepatocarcinoma-22(H₂₂) implantation.Methods Forty Kunming mice were randomly divided into four groups:model group and aplysin treatment groups(25, 50, 100 mg/kg^-1/d^-1) and H₂₂ cells were inoculated subcutaneously into left anteromedial of the mice of all the groups.Except for the model group, all the mice in the other 3 groups were treated with aplysin of different dosage by gavage on the second day and sacrificed after 15 days.We weighed the tumor tissue and calculated the tumor inhibition rate.The expressions of matrix metalloproteinases-9(MMP-9), vascular endothelial growth factor(VEGF), and proliferating cell nuclear antigen(PCNA) in tumor tissue were determined simultaneously with immunohistochemistry.And the levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in serum were measured with enzyme-linked immunosorbent assay(ELISA).Results Aplysin decreased the tumor weight significantly in a dose-dependent manner, with the tumor inhibition rates of 28.31%, 33.84%, and 42.96%, respectively.For the mice with aplysin treatment at the concentrations of 50 and 100 mg/kg^-1/d^-1, the expressions of MMP-9 were 54.29±6.41% and 29.31±3.15%, and were significantly different from that of model group(74.80±8.06%).The expressions of VEGF and PCNA were obviously inhibited in a dose-effect mamer(P<0.05).In moderate and high-dose asplysin treatment groups, the level of IL-6 in serum were 0.34±0.050 and 0.37±0.04 and the TNF-α were 1.26±0.21 and 1.49±0.17, which were significantly higher than those of model group(P<0.05).Conclusion Aplysin could inhibit tumor growth by suppressing extracellular matrix degradation and angiogenesis and improving the immune capacity in mice.