Objective To investigate the efficacy and adverse reactions of amoxicillin clavulanate potassium combined with anti-tuberculosis drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB) in young patients for providing reference for the treatment of MDR-TB. Methods 107 MDR-TB patients were randomly divided into control group (n = 52) and observation group (n = 55). The control group was treated with conventional anti-tuberculosis drugs, which was given levofloxacin, isoniazid aminosalicylate, amikacin, prothionamide and ethambutol. The observation group received amoxicillin clavulanate potassium based on the same medication of the control group. The treatment course of the two groups was 18 months. The change of sputum negative conversion, lesion absorption, cavity closure and adverse reactions were observed and compared between the two groups. Results At the end of the third, ninth, twelfth and eighteenth month, the sputum negative rates were respectively 52.73%, 67.27%, 76.36% and 85.45% in the observation group, which were significantly higher than those in the control group by 32.69%, 46.15%, 57.69% and 65.38% (P<0.05). At the end of the treatment course, the rates of lesion absorption and cavity closure in the observation group were respectively 87.27% and 74.55%, which were significantly higher than those in the control group by 67.31% and 44.23% (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion It was effective and safe that amoxicillin clavulanate potassium was combined with anti-tuberculosis drugs in the treatment of MDR-TB in young patients.