Objective <p>To investigate the value of fibro-bronchoscopic cryosurgery combined with medication in the treatment of tracheobronchial tuberculosis (TBTB).</p> Methods <p>This study was designed as a prospective, randomized clinical trial. 96 patients with newly diagnosed TBTB were collected and divided into the study group (<i>n</i> = 48) and the control group (<i>n</i> = 48). Specifically, conventional anti-tuberculosis therapy was given to the control group, with the study group undergoing fibro-bronchoscopic cryosurgery combined with topical administration. Afterward, the post-treatment response rate and adverse reaction indicators were collected for comparison.</p> Results <p>After treatment for 6 months, the study group was superior to the control group in terms of clinical efficacy (<i>P</i> = 0.013), negative conversion rate of acid-fast bacilli (<i>P</i> = 0.014), and lesion recovery (<i>P</i> = 0.003); after treatment for 6 months, the study and control groups exhibited no significant differences in the response rate of inflammatory infiltration (<i>P</i> = 1.000) and granulation proliferation (<i>P</i> = 0.061). Additionally, the study group showed a higher response rate of ulcer necrosis (<i>P</i> = 0.041) and cicatricial stenosis (<i>P</i> = 0.029) than the control group, with no significant differences observed in the incidence of adverse reactions between the 2 groups (<i>P</i> = 0.584). Moreover, the clinical efficacy in the study group was higher than that in the control group after treatment for 12 months (<i>P</i> &lt; 0.001).</p> Conclusion <p>The application of fibro-bronchoscopic cryosurgery combined with topical administration on the basis of conventional anti-TB treatment can improve the clinical efficacy of TBTB patients and shorten the duration of treatment without increasing the incidence of adverse reactions.</p>