Objective: To investigate the relationship between serum amylase (AMY), cystatin C (CysC) and prognosis of patients with cardiogenic shock after extracorporeal membrane oxygenation (ECMO). Methods The clinical data of 97 patients with cardiogenic shock treated in our hospital from June 2020 to May 2023 were retrospectively collected. All patients were treated with ECMO, and relevant laboratory indicators were examined before ECMO was put on the computer. Patients were divided into successful group and failed group according to their survival within 28 days after withdrawal. The serum AMY and CysC levels were analyzed and compared between the two groups before computer. Logistic regression was used to analyze the relationship between serum AMY and CysC and the prognosis of ECMO in patients with cardiogenic shock. Receiver operating characteristic (Roc) curve was drawn to analyze the predictive value of serum AMY and CysC for ECMO treatment in patients with cardiogenic shock. Results Among 97 patients, 54 cases succeeded and 43 cases failed. The acute physiological and chronic health scores (APACHEⅡ), serum AMY, CysC and lactate dehydrogenase (LDH) expressions in the failed group were significantly higher than those in the successful group (P < 0.05). Logistic regression analysis showed that failure of withdrawal after ECMO treatment in patients with cardiogenic shock was associated with increased APACHE Ⅱ score, serum AMY, CysC, LDH expression (P < 0.05). Roc curve was drawn, and the AUC of serum AMY and CysC for predicting the outcome of withdrawal after ECMO treatment in patients with cardiogenic shock was 0.795 and 0.795, and the optimal cut-off value was 315.000 (U.L-1) and 14.880 (mg.L-1). Conclusion The failure of ECMO withdrawal in patients with cardiogenic shock may be related to the increase of serum AMY and CysC expression. The detection of serum AMY and CysC expression before ECMO withdrawal can predict the outcome of ECMO withdrawal.