Infection with tuberculosis (TB) has been a leading cause of death worldwide. The accurate detection of Mycobacterium tuberculosis (M. tuberculosis) is integral for the prevention and control programs for TB disease. Host-encoded microRNAs (miRNAs) are known to be triggered upon TB infection, raising possibilities of their utility as biomarkers. Here, we investigated the value of miRNAs in pointing active TB (ATB) and predicting the progression from latent TB (LTB) to ATB infection. We then constructed signaling pathways predicted to be involved in TB disease pathobiology. Our analyses identified miR-21-5p, miR-29a-3p and miR-361-5p as being down regulated in ATB and upregulated in LTB compared to healthy subjects with an area under the curve (AUC) of > 0.9, indicating potentially promising biomarker. Pathways related to estrogen signaling, TNF and apoptosis signaling were enriched targets for those miRNAs. This study provides evidence for the significance of miRNA as diagnostic and prognostic markers for ATB and LTB infections in humans. These results could be extrapolated and validated using future large-scale studies.