Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Methods Cell counts,cell cycle distribution,the percentage of lymphocytes subsets and the levels of IL-2 were measured,and two-dimensional gel electrophoresis(2-DE) was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice. Results Compared with the normal group,the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whole spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3+ T lymphocytes and CD8+ T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Meanwhile,the IL-2 level was also higher in the tumor-bearing group than in the normal group. Furthermore,two dysregulated protein,β-actin and S100-A9 were identi?ed in spleen lymphocytes from H22-bearing mice,which were closely related to cellular motility. Conclusion It is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen,which may explain the underlying cause of splenomegaly in H22-bearing mice. Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Cell cycle distribution, the percentage of lymphocytes subsets and the levels of IL-2 were measured, and two-dimensional gel electrophoresis -DE) was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice. Results Compared with the normal group, the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whole spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3 + T lymphocytes and CD8 + T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Mean while, the IL-2 level was also higher in the tumor-bearing group than in the normal group. which, both were also higher in the tumor-bearing group than in the normal group. closely related to cellular motility. Conclusion It is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen, which may explain the underlying cause of splenomegaly in H22-bearing mice.