OBJECTIVE： To compare the efficacy and safety of levofloxacin and moxifloxacin in the treatment of patients with drug-resistant tuberculosis. METHODS： 148 patients with drug-resistant tuberculosis were divided into observation group（74 cases） and control group（74 cases）. All patients were treated with 300 mg Aminosalicylic acid isoniazid tablet+250 mg Ethambutol hydrochloride tablet+200 mg Pyrazinamide tablet+200 mg Protionamide tablet，3 times a day， treatment for 3 months； based on it， observation group was orally given 0.4 g Moxifloxacin hydrochloride tablet， once a day； control group was orally given 0.5 g Levofloxacin hydrochloride tablet， once a day. They were treated for 12 months. The total efficacy， sputum negative convevsion rate after 1，4，8 and 12 months， X-ray cavities lesion improvement and incidence of ADR in 2 groups were observed. RESULTS： The total efficacy， sputum negative conversion rate after 1， 4， 8 and 12 months， and cavity closure and reduced proportion in observation group were significantly higher than control group， the empty change and increase proportion， incidence of ADR were significantly lower control group， the differences were statistically significant （P＜0.05）. CONCLUSIONS： Based on conventional treatment， moxifloxacin shows better efficacy and safety than levofloxacin in the treatment of patients with drug-resistant tuberculosis.