Tuberculosis (TB) is a severe infectious disease that seriously endangers human health. The immune defence mechanism of the body against TB is still unclear. The purpose of this study was to find the key molecules involved in the immune defence response during TB infection, and provide reference for the treatment of TB and further understanding of the immune defence mechanism of the body. Data from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456 were downloaded from GEO data sets for analysis, and a total of 192 differentially expressed genes were screened out. Most of these genes are enriched in the interferon signalling pathway and are defence response–related. We also found that STAT1 plays an important role in the immune defence of TB infection and it is one of the key genes related to interferon signalling pathway. STAT1‐related molecules including hsa‐miR‐448, hsa‐miR‐223‐3p, SAMD8_hsa_circRNA 994 and TWF1_hsa_circRNA 9897 were therefore screened out. Furthermore, expression levels of hsa‐miR‐448 and hsa‐miR‐223‐3p were then verified by qRT‐PCR. Results showed that both hsa‐miR‐448 and hsa‐miR‐223‐3p were down‐regulated in plasma from patients with pulmonary TB. Taken together, our data indicate that an mRNA‐miRNA‐circRNA interaction chain may play an important role in the infection of MTB, and STAT1 and related molecules including hsa‐miR‐223‐3p, has‐miR‐448, SAMD8_hsa_circRNA994 and TWF1_hsa_circRNA9897 were identified as potential biomarkers in the development of active TB.