Abstract: OBJECTIVE To explore the risk factors for death of the immune system disease patients complicated with tuberculosis so as to provide bases for early clinical identification of high-risk patients. METHDOS Totally 129 immune system disease patients who were complicated with tuberculosis and treated in Zhoukou Infectious Disease Hospital from Feb. 2021 to Dec. 2025 were retrospectively enrolled in the study and were divided into the death group with 31 cases and the survival group with 98 cases according to the follow-up outcomes. The demographic characteristics, clinical characteristics and clinical laboratory test indicators were collected from the enrolled patients. Univariate analysis and multivariate analysis were performed by Cox proportional risk regression model, the hazard ratio (HR) and 95% confidence interval (CI) were calculated, and the survival curves were drawn through Kaplan-Meier method. RESULTS Among the 129 patients, 31 (24.03%) died. Univariate Cox regression analysis indicated that the complication with non-tuberculosis Mycobacterium (NTM) was associated with the death (HR=4.13,95%CI:1.27 to 13.35,P=0.012). Multivariate Cox regression analysis showed that the resistance to rifampicin (HR=2.36,95%CI:1.04 to 5.36,P=0.041) and complication with NTM disease(HR=5.76,95%CI:1.49 to 22.34,P=0.011) were the independent risk factors for the death, and the presence of 1 to 3 pulmonary cavities (HR=0.49,95%CI:0.27 to 0.90,P=0.021) was the independent protective factor for death. CONCLUSIONS The resistance to rifampicin and complication with NTM disease are the independent risk factors for the death of the immune system disease patients complicated with tuberculosis, whereas the presence of a limited number of pulmonary cavities may be associated with the more favorable survival outcome.