Objective To study and analyze the correlation between serum long non coding RNA human leukocyte antigen complex group 11 （LncRNA HCG11） and microRNA（miR）-26b-5p levels with cerebral infarction area and functional prognosis in patients with acute ischemic stroke. Methods From January 2021 to December 2022， 106 patients with acute ischemic stroke admitted to our hospital were collected. They were separated into the small area group， the medium area group， and the large area group based on the infarct size. After one year of follow-up， patients were categorized into a good prognosis group and a poor prognosis group based on the modified Rankin Scale （mRS）. QRT-PCR was applied to detect the relative expression levels of LncRNA HCG11 and miR-26b-5p. Logistic regression was applied to analyze the factors that affected the infarct size and prognosis of patients. Receiver operating characteristic （ROC） curve was plotted to analyze the diagnostic value of LncRNA HCG11， miR-26b-5p for infarct size and prognosis. Spearman correlation was used to analyze the correlation of LncRNA HCG11 and miR-26b-5p with infarct size and National Institutes of Health Stroke Scale （NHISS）. Results The level of LncRNA HCG11 increased and the level of miR-26b-5p decreased in patients with large area acute ischemic stroke infarction （P < 0.05）. Compared with patients with good prognosis， patients with poor prognosis had higher level of LncRNA HCG11 and lower level of miR-26b-5p （P < 0.05）. There were statistically significant differences （P < 0.05） in the history of hypertension， hyperlipidemia， NHISS scores， and C-reactive protein （CRP） levels among patients with different infarct sizes. LncRNA HCG11 was positively correlated with both infarct size and NHISS （r_梗死面积 = 0.553， r_NHISS =0.462， P < 0.001）， and miR-26b-5p was negatively correlated with both infarct size and NHISS （r'_梗死面积 = -0.534， P'_梗死面积< 0.001；r'_NHISS = -0.447， P'_NHISS< 0.001）. MiR-26b-5p was a protective factor that poor prognosis in patients. Hypertension history， NHISS score， CRP， and LncRNA HCG11 were risk factors for poor prognosis in patients （P < 0.05）. LncRNA HCG11 and miR-26b-5p and the combined diagnosis of infarct size in patients was superior to the diagnosis of separate indicators （Z_{LncRNA HCG11} = 3.049，P_{LncRNA HCG11} = 0.002；Z_miR-26b-5p = 2.657，P_miR-26b-5p = 0.008，AUC=0.937）. LncRNA HCG11+miR-26b-5p predicted patient prognosis significantly better than LncRNA HCG11， miR-26b-5p， CRP， NHISS alone （Z_{LncRNA HCG11} = 2.207， P_{LncRNA HCG11}= 0.027； Z_miR-26b-5p= 2.080， P_miR-26b-5p= 0.038； Z_CRP = 2.341， P_CRP = 0.019； Z_NHISS = 2.093， P_NHISS= 0.036， AUC=0.892）. LncRNA HCG11 was negatively correlated with miR-26b-5p （r= -0.425， P<0.05）. Conclusion Serum LncRNA HCG11 level increased and miR-26b-5p level decreased in patients with acute ischemic stroke， both of which were influencing factors on cerebral infarct size and functional prognosis， and showed certain diagnostic and predictive value for cerebral infarct size and functional prognosis.