Objective To discuss the correlation between serum hypoxia inducible factor 1alpha （HIF-1α）， soluble leukocyte differentiation antigen 40 Ligand （sCD40L）， chemokine CC motif ligand 3 （CCL3） levels and the infarction site and neural dysfunction in patients with acute cerebral infarction. Methods A total of 80 patients with acute cerebral infarction treated in our hospital from January 2015 to January 2018 were selected as the observation group， and 65 healthy patients in our hospital were selected as the control group. The correlation between serum HIF-1α，sCD40L，CCL3 and infarct site and neurological dysfunction was analyzed. Results Serum levels of HIF-1α， sCD40L and CCL3 in the observation group were significantly higher than those in the control group （P＜ 0.05）. Serum levels of HIF-1α， sCD40L and CCL3 in subcortical infarction group were significantly higher than those in cortical infarction group （P＜ 0.05）. Serum levels of HIF- 1α， sCD40L and CCL3 in patients with severe neurological impairment were significantly higher than those in patients with mild and moderate neurological impairment （P＜0.05）. When the infarction site and nerve function defect were taken as dependent variables， and serum HIF-1α， sCD40L and CCL3 were taken as independent variables， the correlation analysis results showed that serum HIF-1α， sCD40L and CCL3 were positively correlated with the infarction site and nerve function defect （P ＜ 0.05）. Conclusions In patients with acute cerebral infarction， there is a close relationship between the expression of HIF-1 alpha， sCD40L and CCL3 and the severity of the disease， which can promote the progression of the disease.