Objective To study the computed tomograhpy (CT) features of non-tuberculous mycobacteria (NTM) and multidrug-resistant pulmonary tuberculosis (MDR-TB), and to improve the differential diagnosis of the disease. Methods The CT imaging data of 67 patients diagnosed with NTM pulmonary disease (NTM lung disease group) and 103 patients with MDR-TB (MDR-TB group) were selected from January 2010 to December 2015 in our hospital. The imaging findings and differences in lesion location were compared between two groups. Results Lesions of NTM lung disease occurred in the posterior segment of the posterior and posterior lumbar dorsal (Ⅰarea), clustered lobular central nodules, accompanied by bronchiectasis and subpleural thin wall empty, rare bronchial foci. MDR-TB lesions occurred in the middle lobe of the right lung and the upper lobe of the left lung (Ⅱarea). The upper lung of the lungs were patch, nodules and caseous lesions, with thick wall and chronic lung inflammation, showing thick wall empty, pulmonary consolidation, atelectasis, calcification (lung), hilar mediastinal lymph node calcification, lung volume reduction, pleural thickening and pleural effusion. Conclusion Chest CT images are similar in NTM lung disease and MDR-TB, but there are differences. The detailed analysis of image features can provide a basis for clinical differential diagnosis.