Objective To analyze the predictive value of α-Hydroxybutyrate dehydrogenase (α-HBDH) combined detection soluble E-cadherin (SE-CAD) levels for chemotherapy prognosis in patients with acute myeloid leukemia (AML). Methods A total of 86 patients with AML admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2021 to June 2023 were selected as the study group, and another 86 healthy individuals who underwent physical examinations during the same period were selected as the control group. After three cycles of decitabine treatment, patients with AML were divided into complete remission (n=28), partial remission (n=37) and non remission (n=21), and patients were divided into good prognosis (n=65) and poor prognosis (n=21) followed up for 9 months. The levels of serum α-HBDH and SE-CAD were compared in patients with different treatment outcomes and prognosis at admission between the two groups. The predictive value of combined detection of serum α-HBDH and SE-CAD levels on the prognosis of AML patients undergoing chemotherapy was analyzed using receiver operating characteristic (ROC) analysis. Results The levels of serum α-HBDH and SE-CAD in the study group were significantly higher than those in the control group at admission (P<0.05). Upon admission, the levels of serum α-HBDH and SE-CAD were compared, with complete remission < partial remission < no remission (P<0.05). The levels of serum α-HBDH and SE-CAD in patients with poor prognosis were significantly higher than those in patients with good prognosis at admission (P<0.05). The area under the curve (AUC) of serum α-HBDH and SE-CAD levels alone and in combination for predicting poor prognosis at admission were 0.642, 0.674, and 0.777, respectively. The combined detection of the two indicators was significantly higher than the detection of each indicator alone. Conclusion The levels of serum α-HBDH and SE-CAD are correlated with the clinical efficacy and prognosis of patients with AML. The detection of their levels have a certain guiding role in the clinical evaluation of the efficacy and prognosis of patients, and can be applied as an auxiliary index for the prognosis evaluation of AML.