Background <p>The risk factors for HIV-positive <i>Talaromyces marneffei</i> patients (HTM) with <i>T.marneffei</i> bloodstream infection (TM BSI) remain unclear. We retrospectively analyzed the independent risk factors for HTM with TM BSI.</p> Methods <p>A retrospective analysis of the clinical records of HTM was conducted. Patients were stratified into TM BSI and non-TM BSI groups on the basis of blood culture results. Clinical characteristics and prognoses were compared between the groups. The study employed multivariate logistic regression to find independent determinants associated with TM BSI development among HTM.</p> Results <p>Among the HTM, statistically significant between-group differences were observed in the incidence of fever, <i>Pneumocystis jirovecii</i> pneumonia, and laboratory parameters including neutrophil percentage, hemoglobin, platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST ratio, albumin, total bilirubin, C-reactive protein, and CD4⁺ T cell count. Compared with non-TM BSI patients, TM BSI patients had elevated 28-day mortality rates. Logistic regression analysis revealed that the neutrophil percentage, platelet, AST, and CD4⁺ T cell count were independent predictors of TM BSI in HTM. The predictive equation derived from multivariate analysis was as follows: Logit(p) = -2.336 + 0.053×neutrophil percentage − 0.011×platelet + 0.02×AST − 0.019×CD4⁺ T cell. This equation exhibited strong predictive performance with an AUC of 0.909 (95% CI: 0.861–0.957).</p> Conclusions <p>This research confirmed that the neutrophil percentage, platelet, AST, and CD4⁺ T cell count were the independent risk factors for TM BSI in HTM. The predictive model incorporating these four parameters exhibited excellent clinical utility for the early identification of TM BSI. These findings may assist clinicians in prognostic evaluation and timely intervention for patients with HTM.</p>