Objective To explore the clinical value of combined detection of neuron specific enolization enzyme (NSE) and homocysteine (HCY) in the diagnosis of cerebral infarction. Methods The serum NSE and HCY levels in 120 patients with cerebral infarction and normal control were detected respectively and the results were used to analyze its relationship with cerebral infarction. Results The serum NSE and HCY levels in patients with cerebral infarction were significantly higher than that of controls (P < 0.05). The serum NSE and HCY levels in patients with large area cerebral infarction were higher than that of in smaller cerebral infarction area group (P < 0.05). The positive rate of NSE and HCY in cerebral infarction group was obviously higher than that of normal control group. The positive rate of combined detection of NSE and HCY were 91.6% and higher than that of single detection. Conclusion The combined detection of serum NSE and HCY play an important role in the diagnosis of cerebral infarction development. They can be used in the early diagnosis, the disease severity and prognosis evaluation of patients with cerebral infarction.