Objective To observe the expression and correlation of miR-181b, E-selectin, soluble isoform of suppression of tumor necrosis 2 (sST2) in acute heart failure (AHF). Methods Seventy-five AHF patients who received treatment in Zhenping county people's Hospital from January 2021 to January 2022 were selected as the AHF group research objects, and 61 healthy people were selected as the control group research objects in the same period. miR-181b was determined by fluorescence quantitative polymerase, and E-selectin and sST2 were detected by enzyme-linked immunosorbent assay. Results Compared with the control group, miR-181b decreased and E-selectin and sST2 increased in AHF group (P<0.05). Compared with grade Ⅱ of cardiac function, miR-181b decreased and E-selectin and sST2 increased in grade Ⅲ and Ⅳ of cardiac function (P<0.05). Compared with grade Ⅲ of cardiac function, miR-181b decreased and E-selectin and sST2 increased in grade Ⅳ of cardiac function (P<0.05). There was a negative correlation between miR-181b and E-selectin (r=-0.539、P=0.001). There was a negative correlation between miR-181b and sST2 (r=-0.439、P=0.001). There was a positive correlation between E-selectin and sST2 (r=-0.439、P=0.001). miR-181b, E-selectin and sST2 were the risk factors affecting the occurrence of AHF (P<0.05). Compared with the single diagnosis of miR-181b, E-selectin and sST2, the value of combined diagnosis in the diagnosis of AHF was higher (P<0.05). Conclusion In AHF patients, miR-181b is low in expression, E-selectin and sST2 are high in expression, and the above indicators are related to the non concentric functional grade, which are detection factors for the occurrence of AHF.