Use of microRNAs is a promising area for non-invasive diagnosis of pulmonary tuberculosis (TB). Herein, we aimed to investigate the diagnostic potential of miR-146a and miR-155 in pulmonary TB and their predictive potential for patient treatment outcomes. The study included 60 patients with active TB, 50 patients with latent TB, and 50 individuals without TB infection. The patients with active TB were given standard treatment regimens and followed up for treatment outcomes. The serum and sputum expression levels of miR-146a and miR-155 were quantified by qRT-PCR. The patients presenting active TB had highest relative expressions of miR-146a and miR-155 in the serum and sputum compared to patients presenting latent TB and healthy volunteers (p <
0.0001). When miR-146a and miR-155 levels in the serum and sputum as tools to diagnose TB, all values of area under the receiver operating characteristics curve (AUROC) were beyond 0.9. The patients with active TB and presenting unfavorable treatment outcomes were demonstrated with higher relative expressions of miR-146a and miR-155 in the serum and sputum than those presenting favorable treatment outcomes (p <
0.0001). When these two miRNAs as tools to predict treatment outcomes, values of AUROC were beyond 0.85. The study unveils detections of miR-146a and miR-155 in the serum and sputum may be a promising non-invasive method to diagnose TB and further to predict treatment outcomes following anti-TB treatment.