To investigate the relationship between serum EphA2 protein concentration and the prognosis of limb dysfunction in patients with acute cerebral infarction (ACI), and analyze the mechanism of blood oxygenation leve1 dependent functional magnetic resonance imaging (BOLD-f MRI) and diffusion tensor imaging(DTI) imaging changes. Methods We selected 126 patients with ACI limb dysfunction in our hospital. After 3 months of treatment, 86 cases had a good prognosis and 40 cases had a poor prognosis. Compare the clinical data of patients with different prognosis, BOLD-f MRI, DTI imaging index, serum EphA2 protein concentration, analyze the correlation between serum EphA2 protein concentration and BOLD-f MRI, DTI imaging index, and the evaluation value of indicators and serum EphA2 protein concentration on the prognosis of patients with ACI limb dysfunction. atients. Results The age, obesity, emotional state, NIHSS score, CST type of patients and MAS and FMA scores 30 days after admission with poor prognosis ACI limb dysfunction were compared with those with good prognosis, and the difference was statistically significant (P＜0.05); poor prognosis patients were on the 3rd day of onset and at the end of the third month of onset Anisotropy score (FA) value, walking area FA (rFA) value, primary sensorimotor area (SMC), auxiliary motor area (SMA), premotor area (PM), posterior parietal cortex (PPC) lowfrequency oscillation amplitude (ALFF) were lower than those with good prognosis, and the serum EphA2 protein concentration was higher than that of patients with good prognosis, and the difference was statistically significant (P＜0.05). Serum EphA2 protein concentration and FA value, rFA, SMC, SMA, ACI limb dysfunction patients ALFF of PM and PPC were negatively correlated (P＜0.05). FA value, rFA, SMC, SMA, PM, ALFF of PPC, and serum EphA2 protein concentration were used to assess ACI limb dysfunction on the 3rd day of onset and at the end of the third month. The prognosis has certain application value. Among them, the AUC of the combined evaluation of the patient's prognosis by the indicators at the end of the third month of onset is the largest, which is 0.926. Conclusion Serum EphA2 protein level is closely related to BOLD-f MRI and DTI imaging characteristics of patients with ACI limb dysfunction. Serum EphA2 protein concentration and BOLD-f MRI and DTI imaging tests before and after treatment are helpful for clinical assessment of the patient’s disease outcome.