Objective To understand the risk and related influencing factors of death of patients with infection of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in Shaoyang City. Methods The survival status and death risk of HIV/AIDS patients in Shaoyang City from 1997 to 2024 were analyzed by Kaplan-Meier survival analysis and Cox proportional hazards regression model of retrospective cohort study method. Results A total of 5 805 patients were included in analysis, 1 941 died during the observation period, out of which 54.20% died from diseases irrelevant to AIDs, and the all-cause mortality was 9.01/100 person-year. The risk of death for males was 1.447 times of females. The comparison of death risk among patients with different ages of HIV infection diagnosis and educational levels showed statistically significant differences (all P<0.05). The death risk of patients with baseline CD4⁺T lymphocyte count in the 0-199 group was 1.497 times higher than that in the ≥500 group (P<0.001), and the mortality in this group was higher than those in other groups. Patients with lower last CD4⁺T lymphocyte counts had a higher risk of death(P＜0.001). The mortality of patients who did not receive antiviral treatment was 36.37/100 person-year, which was higher than 4.21/100 person-year of those who received treatment. The maximum ratio of death risk between the two was 6.578 (P<0.001). Compared with patients in the INSTI-containing regimen group, the death risks of patients in LPV/r-containing and NNRTI-containing regimen groups were 4.902 and 2.769, respectively (both P<0.001), and patients in the LPV/r-containing regimen group had a higher percentage of deaths due to cardiovascular and cerebrovascular diseases than those in the NNRTI regimen group (11.79% vs 7.26%; χ²=3.872, P=0.049). Conclusion HIV/AIDS patients in Shaoyang City face a high risk of death. Male, advanced age, low educational level, without receiving antiviral treatment, and low baseline/last CD4⁺T lymphocyte count are all important factors that contribute to the increase of death risk. Receiving INSTI-containing treatment regimen can significantly reduce mortality. Therefore, early detecting cases, timely optimizing antiviral treatment regimen, as well as strengthening patient management and compliance education have certain clinical reference value for reducing the risk of death in HIV/AIDS patients.