Abstract Objective To investigate the value of CEUS in percutaneous needle biopsy of anterior mediastinal masses. Methods 79 patients with anterior mediastinum, 39 of whom underwent CEUS before the biopsy were the experimental group, and 40 received only routine ultrasound as the control group. The number of samples and pathological diagnosis were analyzed between the two groups. Rate and rate of necrosis in the lesion. Results The liquefaction necrosis rates in the experimental group and the control group were 66.67% (26/39) and 22.50% (9/40), respectively, and the difference was statistically significant (P<0.05). The pathological diagnosis rates of the experimental group and the control group were respectively 94.87% (37/39) and 77.50% (31/40), the difference was statistically significant (P<0.05). The number of punctures in the experimental group and the control group were (2.05±0.32) times and (2.00±0.00 times), and the difference was not statistically significant (P>0.05). No serious complications were seen in either group. One patient in CEUS had a subcutaneous hematoma after puncture, and no serious complications were found in the control group. Conclusion CEUS can identify the necrotic area and active area in the lesion, and improve the safety, accuracy and success rate of biopsy.