Objective: To investigate the expression of transforming growth factor-β1 (TGF-β1) in the splenic tissues from patients with hypersplenism induced by portal hypertension (PH), idiopathic thrombocytopenic purpura (ITP) and hemolytic anemia (HA) respectively and its role in splenic fibrosis. Methods: According to the etiopathogenisis, the splenectomy specimens were divided into group A (PH or cirrhosis induced hypersplenism), group B (ITP induced hypersplenism), group C (HA induced hypersplenism) and group D (traumatic rupture of the spleen as the control), with 20 cases in each group. The morphological features of the specimens were observed through HE and Mason staining, and their TGF-β1 expressions were detected by Western blot analysis. Results: The HE and Mason staining showed that the splenic tissues of group A, B and C all presented different degrees of fibrosis, and that in group A had the most severe fibrosis, but no fibrotic change was noted in the specimens of group D. Western blot showed that the TGF-β1 expressions of the group A, B and C were all significantly higher than that of the group D (all P<0.05), but these had no statistical differences among the group A, B and C (P>0.05). Conclusion: There is overexpression of TGF-β1 in splenic tissue of the patients with hypersplenism, and it may be one of the mechanisms for the severe splenic fibrosis in these patients.