OBJECTIVE: To discuss and analyze the expression and clinical significance of serum alpha-fetoprotein (AFP), P-selectin (P-sel), and matrix metalloproteinase-9 (MMP-9) in hepatic sclerosis combined with portal vein thrombosis (PVT). STUDY DESIGN: In this retrospective study, 38 patients with hepatic sclerosis combined with PVT diagnosed from August 2010 to February 2018 were chosen as the observation group. During the same period, 120 hepatic sclerosis patients without PVT were chosen as the control group. The serum AFP, P-sel, and MMP-9 expression levels of both groups were detected. Meanwhile, the expression levels of AFP, P-sel, and MMP-9 in liver tissue samples of the 2 groups were detected using the Elivision immunohistochemical method. The correlation and clinical significance of AFP, P-sel, and MMP-9 were evaluated. RESULTS: In the observation group there were 9 cases with splenectomy (23.7%) and 13 with diabetes (34.2%). In the control group there were 3 cases with splenectomy (2.5%) and 14 with diabetes (11.7%). The comparison differences showed statistical significance (p<0.05). The levels of serum AFP, P-sel, and MMP-9 in the observation group were higher than those in the control group, and the difference was statistically significant (p<0.05). Among the 158 patients the best diagnostic thresholds for AFP, P-sel, and MMP-9 in the diagnosis of cirrhosis with PVT were 25.22 IU/mL, 292.22 ng/mL, and 372.43 ng/mL, respectively, and the AUC values were 0.779, 0.722, and 0.755, respectively. Multivariate logistic regression analysis showed that AFP (OR=2.244), P-sel (OR=3.179), and MMP-9 (OR=2.508) were the main risk factors for PVT (p<0.05). The expression level of AFP was positively correlated with the expression of P-sel and MMP-9 in hepatic sclerosis patients with PVT. CONCLUSION: Serum AFP, P-sel, and MMP-9 present high expression in hepatic sclerosis combined with PVT, with high diagnosis sensitivity and specificity, and may have synergistic effect on the pathogenesis leading to PVT. © Science Printers and Publishers, Inc.