Our study aimed to develop and validate a nomogram to assess talaromycosis risk in hospitalized HIV-positive patients. Prediction models were built using data from a multicentre retrospective cohort study in China. On the basis of the inclusion and exclusion criteria, we collected data from 1564 hospitalized HIV-positive patients in four hospitals from 2010 to 2019. Inpatients were randomly assigned to the training or validation group at a 7:3 ratio. To identify the potential risk factors for talaromycosis in HIV-infected patients, univariate and multivariate logistic regression analyses were conducted. Through multivariate logistic regression, we determined ten variables that were independent risk factors for talaromycosis in HIV-infected individuals. A nomogram was developed following the findings of the multivariate logistic regression analysis. For user convenience, a web-based nomogram calculator was also created. The nomogram demonstrated excellent discrimination in both the training and validation groups [area under the ROC curve (AUC) = 0.883 vs. 0.889] and good calibration. The results of the clinical impact curve (CIC) analysis and decision curve analysis (DCA) confirmed the clinical utility of the model. Clinicians will benefit from this simple, practical, and quantitative strategy to predict talaromycosis risk in HIV-infected patients and can implement appropriate interventions accordingly.