Objective To investigate the early diagnostic value of heparin-binding protein (HBP), albumin (ALB) and CD4+T cells in urosepsis after upper urinary tract calculus surgery in HIV/AIDS patients. Methods A retrospective analysis of 102 HIV/AIDS patients with upper urinary tract calculus. After minimally invasive lithotripsy, 31 cases were complicated with urosepsis (observation group) and 71 cases were not complicated with urosepsis (control group). To compare the clinical data of the two groups of patients, analyze the influencing factors of urosepsis after upper urinary tract calculus surgery, and evaluate the predictive value of separate detection of HBP, ALB, CD4+T cell count and combined detection of the above three indicators for urosepsis after upper urinary tract calculus surgery in HIV / AIDS patients. Results Among the 102 patients, 31 patients (30.4%) had urosepsis after surgery (observation group), and 71 patients did not have urosepsis (control group). There were statistically significant differences in gender, stone location, urine culture positivity rate, and urine nitrite positivity rate between the two groups of patients (all P<0.05). At 6 hours after surgery, the level of HBP in the observation group was higher than that in the control group, and the levels of ALB and CD4+T cells were lower than those in the control group (all P<0.05). The result of multivariate Logistic regression analysis showed that gender, positive preoperative urine culture, positive nitrite, increased postoperative HBP level, decreased ALB level, and decreased CD4+T cell count were independent risk factors for urosepsis after surgery in HIV/AIDS patients with upper urinary tract calculus (all P<0.05). When the cut-off values of HBP was 13.5 pg/mL, ALB was 33.05 g/L and CD4+T cell count was 246 cells/μL, the area under the ROC curve for the diagnosis of urosepsis was 0.990, 0.887 and 0.851, respectively; and the area under the curve of the combined detection of HBP, ALB and CD4+T cell count was 0.994 (95%CI: 0.000—1.000, sensitivity 100.00%, specificity 95.77%), and the combined detection had higher sensitivity and negative predictive value. Conclusion HBP, ALB and CD4+T cell count can be used as reliable indicators to predict urosepsis in patients with HIV/AIDS complicated with upper urinary tract calculus after surgery, and the combined detection has higher predictive value.