Objective To explore the value of dual factor combined detection using tuberculosis (TB) specific cytokines interferon-γ (IFN-γ) and interleukin-2 (IL-2) in TB diagnosis in patients with human immunodeficiency virus (HIV) infection, and the influencing factors for underdiagnosis. Methods HIV-infected patients admitted to and underwent TB-related examination in the Department of Infectious Diseases in Hezhou People’s Hospital from July 2022 to September 2024 were collected. According to the clinical diagnosis criteria, patients were divided into the HIV infection with TB group (HIV/TB group) and the HIV infection without TB group (control group). Diagnostic efficacy of dual factor combined detection was evaluated. HIV/TB group was further divided into a true-positive group and a false-negative group based on the detection results. The independent influencing factors for underdia- gnosis was analyzed using multivariate logistic regression. Results A total of 306 patients were included in the analysis, with an average age of (55.69±14.02) years. There were 105 patients in the HIV/TB group and 201 in the control group. The sensitivity and specificity of dual factor combined detection for TB in all HIV-infected patients were 72.4% (76/105) and 87.1% (175/201), respectively. There was a statistically significant difference in sensitivity (χ²=9.488, P=0.009) and no statistically significant difference in specificity (χ²=5.846, P=0.054) among the three CD4⁺T lymphocyte count gradients in the dual factor detection. Among them, patients with CD4⁺T cell count <100 cells/μL had lower sensitivity (58.8%) in dual factor detection than patients with CD4⁺T cell count ≥200 cells/μL (88.9%) and 100-199 cells/μL (81.5%), differences were both statistically significant (both P<0.05). In HIV/TB co-infected patients with CD4⁺T lymphocyte count ≥100 cells/μL, the general sensitivity and the specificity of dual factor combined detection were 85.2% (46/54) and 82.0% (91/111), respectively. Multivariate analysis showed that CD4⁺T lymphocyte count was an independent influencing factor for the underdia-gnosis in HIV/TB patients conducting dual factor combined detection (P<0.05), while age, gender, pathogen results, and the presence or absence of TB had no statistically significant impact on the results of dual factor combined detection (all P>0.05). Conclusion Dual factor combined detection using tuberculosis-specific cytokines IFN-γ and IL-2 has a high diagnostic value in the diagnosis of TB in HIV-infected patients, especially in those with CD4⁺T lymphocyte count ≥100/μL, which can provide auxiliary diagnostic value for the clinical diagnosis of HIV infection combined with TB.