Objective To investigate the predictive value of serum heparin binding protein (HBP) and procalcitonin (PCT) for 28-day mortality risk in patients with sepsis associated acute kidney injury (SA-AKI). Methods A retrospective analysis was performed of the clinical data of 75 SA-AKI patients admitted to the intensive care unit (ICU) of Emergency Department in Shanxi Bethune Hospital from July 2020 to February 2022. They were divided into the survival group (n=51) and death group (n=24) based on 28-day outcome, and the two groups were compared in HBP, PCT and other clinical data. SPSS statistics 26.0 was used for data analysis. Depending on the data type, t-test, Mann-Whitney U test, or χ² test was used for comparison between groups. Univariate analysis and multivariate logistic regression were used to analyze the factors influencing the risk of death at 28 days, and forest plots were drawn to compare the independent prognostic factors. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of 28-day death risk factors. Results The two groups differed significantly in HBP [115.66 (96.88,255.20) vs 95.61(46.82,114.79) ng/ml], PCT [29.13(26.03,111.53) vs 14.41(6.62,23.91) ng/ml], lactic acid [3.90(1.75,6.93) vs 2.02(1.47,4.08) mmol/L], APACHE Ⅱ [25.50 (21.25,31.00) vs 20.00(16.00,26.25) points], SOFA [(11.46±3.68) vs (8.69±3.50) points], hospital stay [9.00(5.50,19.75) vs 21.50(15.00,30.00) d], use of mechanical ventilation support [24(100.0%) vs 35(68.6%)], and use of vasoconstrictor [22(91.7%) vs 32(62.7%)] (P＜0.05). Logistic regression analysis showed that HBP (OR= 1.155, 95% CI 1.007-1.325), PCT (OR=2.698,95% CI 1.003-7.254) and hospital stay (OR= 0.379,95%CI 0.144-0.995) were independent influencing factors for death at 28 days in the SA-AKI patients. ROC curve analysis showed an area under the curve (AUC) of 0.755 for HBP with an optimal cut-off value of 65.815 ng/ml, a sensitivity of 58.3% and a specificity of 78.4%; an AUC of 0.871 for PCT with an optimal cut-off value of 20.670 ng/ml, a sensitivity of 100.0% and a specificity of 64.7%; and an AUC of 0.903 both with an optimal cut-off value of 0.222 ng/ml, a sensitivity of 100.0% and a specificity of 70.6%. Conclusion Elevated serum levels of HBP and PCT were independent risk factors for 28-day death in SA-AKI patients. Serum levels of HBP and PCT have good predictive value for 28-day death in SA-AKI patients, and they predict better in combination than individually.