Objective To explore the diagnostic value of serum Tenascin C (TNC) in Bronchopulmonary dysplasia (BPD) of the premature infants. Methods Seventy-nine very low birth weight premature infants were enrolled from the Department of Neonatology, the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University from 2018 to 2020. According to the 2018 NICHD diagnostic criteria, they were divided into non-BPD group (n = 48) and BPD group (n = 31): (1) ELISA was used to detect serum TNC level; (2) Multivariate Logistic regression analysis of independent risk factors for BPD was conducted; (3) The correlation between serum TNC level and the severity of BPD was analyzed; (4) Receiver Operating characteristic curve (ROC) of TNC for diagnosis of BPD was made. Results 1. The serum TNC level of preterm infants was statistically different between the non-BPD group (95.03±19.73ng/ml) and the BPD group (125.40±19.34ng/ml) (P < 0.001), and there was statistical difference between different levels of BPD groups (P < 0.001). 2. The independent risk factors for BPD in premature infants included inhalation of high concentrations of oxygen, oxygen duration and serum TNC level (P < 0.05). 3. Serum TNC level was positively correlated with the severity of BPD (r =0.7031, P < 0.0001). 4. The area under the curve for the diagnosis of BPD by serum TNC was 0.8807 (P < 0.0001), the sensitivity was 96.8%, and the specificity was 66.7%. Conclusion Serum TNC level increases in BPD, and the diagnostic sensitivity and specificity is high, which can be used as one of the biomarkers for the diagnosis of premature BPD.