Objective To analyze the expression of circular RNAs HECT domain E3 ubiquitin-protein ligase 1 （circ_HECTD1） and miR-372-3p in the serum of patients with acute cerebral infarction （ACI） and their correlation with the severity of brain injury. Methods From January 2018 to January 2021， 100 ACI patients admitted to the Department of Neurology of the First Hospital of Xingtai were selected as the study group， and 96 healthy individuals who underwent physical examinations during the same period were included in the control group. Serum circle_HECTD1 and miR-372-3p levels were measured using quantitative real-time fluorescence PCR （qRT-PCR）. The National Institute of Health Stroke Scale （NIHSS） was used to assess the severity of brain injury in patients， and patients were divided into the mild to moderate group （NIHSS score was from 0 to 15） and the severe group （the score was from 16 to 42） based on the scores. Spearman and Pearson correlation were used to analyze the correlation between the expression levels of serum circ_HECTD1 and miR-372-3p and the NIHSS score. Multivariate Logistic regression was used to analyze the influencing factors of brain injury severity in ACI patients. The value of serum circ_HECTD1 and miR-372-3p expression levels in diagnosing the severity of brain injury in ACI patients was analyzed through the receiver operating characteristic （ROC） curve. Results The serum circ_HECTD1 level in the study group was higher than that in the control group， and the miR-372-3p level was lower than that in the control group， with statistical differences （P＜ 0.05）. Compared with the mild to moderate group （n=67）， the severe group （n=33） had higher serum circ_HECTD1 levels and NIHSS scores， and lower miR-372-3p levels， with statistically significant differences （P＜ 0.05）. Correlation analysis showed that the serum circ_HECTD1 level of patients was positively correlated with NIHSS score （r=0.541， P＜0.05）， while the serum miR-372-3p level was negatively correlated with circ_HECTD1 level and NIHSS score （r=-0.370， -0.426； P＜ 0.05）， and the differences were statistically significant. The area under the ROC curve （AUC） for the combined diagnosis of serum circ_HECTD1 and miR-372-3p in ACI patients with brain injury severity was 0.80 ［95%CI （0.74， 0.86）］. Multivariate Logistic regression showed that the expression levels of serum PCT， circle_HECTD1， and miR-372-3p were statistically significant factors affecting the severity of brain injury in ACI patients （P ＜ 0.05）. Conclusions The serum circ_HECTD1 levels are high and miR-372-3p levels are low in ACI patients， which are closely related to the severity of brain injury in patients.