Objective To investigate the clinical value of soluble endothelial protein C receptor （sEPCR） and von Willebrand factor （vWF） in the severity assessment of patients with acute cerebral infarction （ACI） and their relationship with interleukin-6 （IL-6）.Methods We selected 125 patients with ACI （group A） who were admitted to the Department of Neurology of Yan’an University Affiliated Hospital from January 2017 to January 2019， and 103 people （group B） who had physical examination in the same hospital during the same period. Group A was divided by the severity of ACI into mild group （63 cases）， moderate group （39 cases）， and severe group （23 cases）. We analyzed the clinical value of serum sEPCR and vWF in the diagnosis and prognosis assessment of ACI and their correlation with IL-6.Results The levels of sEPCR， vWF， and IL-6 in group A were significantly higher than those in group B （P<0.05）. With the increase in ACI severity， the levels of sEPCR， vWF， and IL-6 significantly increased （P<0.05）. The levels of sEPCR and vWF had positive correlations with the level of IL-6 and the severity of the disease （P<0.05）.Conclusions sEPCR and vWF are positively correlated with IL-6 and disease severity in ACI. sEPCR and vWF detection may effectively improve the assessment of the severity of ACI.