Objective To analyze the predictive value of cysteine aspartic protease 12 (Capase-12), cysteine aspartic protease 3 (Capase-3) and death related protein kinase 1 (DAPK1) in septic shock in patients with severe sepsis. Methods Ninety patients with severe sepsis treated in our hospital from April 2020 to April 2023 were selected as the observation group, and 90 healthy subjects in our hospital during the same period were selected as the control group. Serum levels of Capase-12, Capase-3 and DAPK1 were compared between the two groups. Observation group was divided into septic shock group (23 cases) and non-septic shock group (67 cases) according to whether septic shock occurred. Serum levels of Capase-12, Capase-3 and DAPK1 were compared between the two groups, receiver operating curve (ROC) was plotted, and area under the curve (AUC) was calculated. To analyze the predictive efficacy of serum Capase-12, Capase-3 and DAPK1 on septic shock. The risk factors of septic shock were analyzed by univariate and multivariate logistic regression. Results The levels of Capase-12, Capase-3 and DAPK1 in the observation group were higher than those in the control group (P＜0.05). The serum levels of Capase-12, Capase-3 and DAPK1 in septic shock group were higher than those in non-septic shock group (P＜0.05). The AUC for the combined detection of serum Capase-12, Capase-3, and DAPK1 in the diagnosis of septic shock was 0.863, and the 95%CI was 0.768-0.952. The sensitivity (95.28%) and specificity (90.76%) were higher than those of single detection (78.19%,72.82%), (75.12%, 70.34%), (72.67%, 68.19%) (P＜0.05). Logistic regression analysis showed that serum Capase-12, Capase-3, DAPK1, number of organ failure, hypoproteinemia, hypovolemia and serum PCT were risk factors for septic shock (P＜0.05).Conclusion Abnormal high levels of Capase-12, Capase-3 and DAPK1 in serum are closely related to the occurrence of septic shock in patients with severe sepsis. Combined detection can improve the predictive efficacy of septic shock. The occurrence of septic shock is related to many factors and should be paid attention to in clinic