Objective: To observe the histopathological manifestations of liver biopsy in patients with hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloid (PA). Methods: Patients diagnosed with PA-HSOS from 2012 to 2017 were selected, and the general conditions, liver function indexes, medication history, liver biopsy time, histopathological slides of liver biopsy, and follow-up data of clinical prognosis after 6 months of onset were collected. Clinical staging with clinical data was used to observe the histopathological manifestations of patients at different clinical stages. Wilcoxon rank-sum test, unpaired t-test and univariate linear regression analysis were used for data analysis. Results: A total of 16 cases were collected. Alanine transaminase and aspartate transaminase was 59.25 U/L and 25.50 U/L, 108 U/L and 45 U/L, respectively, after 6 months of onset and follow-up, and the differences were statistically significant. Moreover, total bile acids and albumin was 35 μmol/L and 36.15 μmol/L, and 32.45 g/L and 31 g/L, respectively, and the differences were not statistically significant. PA-HSOS pathological development process was divided into early, middle and late stages. In the early stage, the central lobular sinusoidal endothelium integrity was impaired and the entry of erythrocytes had interspersed thin reticular fibers and perisinusoidal space. In the middle stage (hemorrhagic zone), erythrocytes, reticular fibers and collagen fibers were lysed, densely collapsed and deposited. The cavity of the bloodstream was hyperemic and dilated, and the cavity was covered with sinus endothelial cells. The hepatic plate regenerated around the hemorrhagic zone and some of the hepatic sinuses were decompensated. In the late stage, deposited collagen in the hemorrhagic zone had formed a large fibrous scar, and most of the dilated cavity in the bloodstream was covered with vascular endothelium. The marginal zone hepatic cells were regenerated in two rows and gradually inserted into the fibrous septum. Different hepatic lobular lesions obtained from the same patients liver biopsy tissues were changed at different stages. Hepatic lobule injury proportion with severe internal bleeding in liver biopsy tissue had no relation with the prognosis of patients. Conclusion: In the early stage of PA-HSOS, erythrocytes in the central zone of lobules enter the perisinusoidal space through the damaged sinus endothelium, which is manifested as hepatic plate hemorrhagic necrosis. In the middle and late stage, liver plate regeneration and vascular remodeling occurred, so most of the patients' clinical course was self-limited. Pathological staging and liver biopsy time have an apparent correlation, but the prognosis of patients cannot be judged based on the extent of hemorrhage and injury of biopsy samples.