Objective To compare and analyze the performances of contrast-enhanced ultrasonography in the diagnosis of pleural-based pulmonary tuberculosis and lung cancer lesions, so as to provide basis for imaging identification. Methods A total of 42 patients with pathologically confirmed pleural-based pulmonary tuberculosis and 42 patients with pleural-based lung cancer admitted to Shanghai Pulmonary Hospital from Jun. 2017 to Feb. 2018 were retrospectively enrolled, and the images of conventional ultrasound and contrast-enhanced ultrasound of the largest lesions in each patient were analyzed. The arrival time, enhancement pattern, enhancement intensity, uniformity, images of necrosis, clearance speed and other characteristics by contrast-enhanced ultrasound were analyzed in the two groups. Results The enhancement patterns of pulmonary tuberculosis and lung cancer were both mainly enhanced from the periphery to the center, but the number of lesions with regular dendritic vascular enhancement in the pulmonary tuberculosis group was significantly more than that in the lung cancer group (10 vs 1; χ²=8.473, P=0.004). Low enhancement was more common in pulmonary tuberculosis lesions (17 vs 6; χ²=7.244, P=0.007), and high enhancement was more common in lung cancer lesions (25 vs 6; χ²=18.456, P<0.001). Compared with the lung cancer group, the necrotic areas in the pulmonary tuberculosis group mostly showed a mesh-like appearance (13 vs 0; χ²=15.380, P<0.001) or regular large patchy necrosis (11 vs 2; χ²=7.372, P=0.007). The necrotic areas in the lung cancer group were more irregular compared with the pulmonary tuberculosis group (16 vs 2; χ²=13.859, P<0.001). The proportion of patients with arrival time<10 s in the pulmonary tuberculosis group was significantly higher than that in the lung cancer group (21 vs 9; χ²=7.467, P=0.006), and the proportion of patients with the arrival time difference<2.5 s compared with normal lung tissue in the pulmonary tuberculosis group was significantly higher than that in the lung cancer group (42 vs 3; χ²=65.227, P<0.001). Conclusion The arrival time difference, enhancement intensity and images of necrosis by contrast-enhanced ultrasound in the pulmonary tuberculosis and lung cancer are significantly different, which can provide evidence for the differential diagnosis of pulmonary tuberculosis and lung cancer.