Objective To study the value of peripheral perfusion index (PPI) combined with acute physiology and chronic evaluation Ⅱ(APACHEⅡ) score in predicting prognosis of septic shock patients. Methods A total of 200 patients diagnosed as septic shock in the emergency department of Xinjiang Medical University First Affiliated Hospital from January to August 2023 were prospectively included. The patients were divided into survival group (84 cases) and death group (116 cases) according to their 28-day prognosis. The patients’ information including name, age, gender, vital signs after admission, Glasgow coma scale(GCS), sepsis-related organ failure assessment(SOFA), APACHEⅡ, infection site, fluid intake within 24 h of admission, antibiotic use, past medical history, types and 24 h doses of vasopressors used, mechanical ventilation status, complete blood count, liver function, renal function, coagulation indicators, onset time, and 28-day prognosis outcomes were recorded. The lactate and PPI values of the two groups of patients were measured at the time of admission (0 h), 6 h after admission, and 12 h after admission, and the lactate clearance rate at 0-6 h and 0-12 h was calculated. Cox regression was used to screen independent factors for predicting the prognosis of septic shock patients, and the area under the ROC curve(AUC) was plotted. PPI parameter combined with APACHEⅡ score were analyzed in predicting AUC, which represented patients’ prognosis. Results Compared with the death group, the survival group had higher GCS score, 0 hPPI, 6 hPPI, 12 hPPI, 0-12 h lactic acid clearance rate, and lower in age, SOFA score, APACHEⅡ score, 0 h lactic acid, 12 h lactic acid (all P<0.05). COX regression showed that 12 hPPI was an independent predictor of the prognosis of patients with septic shock, and the AUC for predicting the prognosis of patients with septic shock was 0.945, and the 12 hPPI combined with APACHEⅡ score for predicting AUC as the prognosis of patients with was 0.996. Conclusions 12 hPPI combined with APACHEⅡ score after admission has good prognostic value for 28-day prognosis of patients with septic shock.