Objective：To investigate the expression and significance of polymorphonuclear myeloid-derived suppressor cells（PMN-MDSC）in patients with hepatitis B virus - related acute -on -chronic liver failure（HBV -ACLF）. Methods：A total of 40 HBV -ACLF patients admitted to Yijishan Hospital of Wannan Medical College from September 2022 to August 2023 were selected as the study group，while 20 patients with chronic hepatitis B（CHB）and 10 healthy controls（HC）diagnosed or undergoing examinations at the same hospital during the same period were collected as the two control groups. Clinical data were collected and blood samples were obtained. Flow cytometry was used to detect the frequency of peripheral blood PMN-MDSC on the day of admission，and to compare the differences in the frequency of PMN-MDSC between the study group and the two control groups. Spearman’s correlation analysis was used to investigate the correlation between the frequency of PMN -MDSC and inflammation markers or disease severity. HBV -ACLF patients were further grouped based on whether they had concurrent or secondary infections and the prognosis on day 28 of follow-up， and the differences in PMN -MDSC frequency among groups were compared. Results：The frequency of PMN -MDSC in HBV -ACLF group was significantly higher than that in the CHB group and the HC group（P ＜ 0.001 for both），whereas there was no significant difference in the PMN-MDSC frequency between the CHB and HC groups（P ＞ 0.05）. The frequency of PMN-MDSC in HBV-ACLF patients was positively correlated with the white blood cell count，neutrophil - to - lymphocyte ratio，procalcitonin，international normalized ratio，total bilirubin，Child -Turcotte -Pugh score，and the model of end - stage liver disease score（r=0.347，0.799，0.506， 0.450，0.462，0.470，0.481，respectively，all P ＜ 0.05），and negatively correlated with the lymphocyte count（r=-0.428，P ＜ 0.01）. Among the 40 HBV-ACLF patients，18 had concurrent infections，17 had secondary infections，and 21 had poor prognosis on day 28， with their peripheral blood PMN - MDSC frequencies significantly higher than those of the control group patients（all P ＜ 0.001）. Conclusion：PMN-MDSC are enriched in HBV-ACLF patients and the frequency of PMN-MDSC in peripheral blood is closely related to infection risk，disease severity，and short-term prognosis of patients.