Objective To explore the factors influencing 2-month sputum smear conversion (2m-SSC) in patients with systemic lupus erythematosus (SLE) and tuberculosis, and to establish a prediction model for 2m-SSC. Methods The initial and follow-up medical records of inpatients with SLE and sputum smear-positive tuberculosis in West China Hospital of Sichuan University from December 2013 to September 2019 were retrospectively reviewed. Single factor analyses and multivariable Firth’s logistic regression were used to determine the influencing factors of 2m-SSC, and a prediction model for 2m-SSC was established. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated to evaluate the performance of the model. Results A total of 91 patients with SLE and sputum smear-positive tuberculosis were ultimately included, with 8 cases in the non-conversion group and 83 in the conversion group. There were statistically significant differences in white blood cell count, total bilirubin, indirect bilirubin (IBIL), triglyceride, and rheumatoid factor (RF) between the two groups (P<0.05). Serum RF [odds ratio (OR)=2.271, 95% confidence interval (CI) (1.312, 4.350), P=0.003], IBIL [OR=2.363, 95%CI (1.206, 5.045), P=0.013], and glucose [OR=2.058, 95%CI (1.016, 4.280), P=0.045] were identified as risk factors unfavorable to 2m-SSC outcomes. The constructed model (including three variables: RF, IBIL, and glucose) had a good ability in predicting 2m-SSC [AUC=0.893, 95%CI (0.744, 1.000)], with a sensitivity of 87.5% and a specificity of 84.3%. Conclusion This study established a prediction model for 2m-SSC in patients with SLE and tuberculosis, and found the value of serum RF, IBIL, and glucose in predicting 2m-SSC, providing certain guidance for clinicians in treatment decisions.