In the current study, we first revealed HupB incubating induced IL-6 releasing in PBMCs from PTB patients, with huge potential for active tuberculosis diagnosis, and constructed a multi-center trial to verify the effectiveness, and the results showed that HupB induced IL-6 release assay has better specificity and sensitivity compared with ESAT-6 and CFP-10 induced IGRA in smear-positive PTB, and better sensitivity in smear-negative PTB patients. Here, IL6 is linked to tuberculosis.