Objective To investigate the expression of microRNAs (miRNAs) in patients with progressive cerebral infarction and its clinical significance.Methods A retrospective analysis was performed on the clinical data of 138 patients with cerebral infarction admitted to our hospital from July 2016 to July 2018. According to the Scandinavian Stroke Scale, the patients were divided into control group (stable cerebral infarction, n=82) and observation group (progressive cerebral infarction, n=56). Patients in the observation group were further divided into three subgroups, i.e., mild progression (n=30), moderate progression (n=17), and severe progression (n=9), according to the score of modified Edinburgh-Scandinavian stroke scale. They were followed up for prognosis two months after discharge and divided into poor prognosis group and good prognosis group. An analysis was performed on the expression of miRNAs in patients with progressive cerebral infarction and its clinical significance.Results Patients with progressive cerebral infarction had significantly higher levels of miRNA-21 and miRNA-223 than those with stable cerebral infarction (P<0.05). The high expression of miRNA-21 and miRNA-223 was a risk factor for progressive cerebral infarction (P<0.05). The severity of progressive cerebral infarction was positively correlated with serum levels of miRNA-21 and miRNA-223 (r=0.834, P=0.008; r=0.896, P=0.001). Patients with poor prognosis had significantly higher expression levels of serum miRNA-21 and miRNA-223 than those with good prognosis (P<0.05); the areas under the receiver operating characteristic curves of serum miRNA-21 and miRNA-223 expression levels in predicting the prognosis of progressive cerebral infarction were 0.805 and 0.834, respectively; the cut-off values were 4.45 (sensitivity=77.14%, specificity=82.28%) and 7.06 (sensitivity=82.86%, specificity=73.42%), respectively.Conclusions Both miRNA-21 and miRNA-223 are highly expressed in patients with progressive cerebral infarction, and their expression levels are positively correlated with the severity of cerebral infarction. In addition, they have high sensitivity and specificity in predicting the prognosis of progressive cerebral infarction, which can be used as biomarkers for early diagnosis and prediction of progressive cerebral infarction.