Abstract: Objective To explore the clinical value of newborn screening based on the targeted capture-based NGS. Methods Using the retrospective dry blood spot samples on the foot of the newborms and the targeted capture-based NGS method, the reported pathogenic sites of the pathogenic genes that cause the 169 conmon inherited diseases of the newborns were detected ，and the pathogenie sites were verified by sanger sequencing. Results It was found that 4 out of 150 samples were suspected positive samples, and the positive rate was 2.67%. 88 cases were pathogenic genes carriers, and the carrying rate of pathogenic genes was about 58.67%. There are no pathogenic gene variants detected in the residual 58 cases. Among them, as many as 40.7% of the samples carrying 1 pathogenic gene variant, and up to 4 different pathogenic gene variants been carried also can be seen. The most frequently carried pathogenic genes were deafiness genes GJB2 and SLC26A4, followed by PAH, SLC22A5, DU0X2, SLC12A3, USH2A and ACADS. Conclusion Newborn screening based on targeted capture-based NGS can expanded the screening of diseases. In addition, the combination and analysis with traditional biochemical screening results can efctively reduce the traditional false-positive rate and improve the positive predictive value which play an important role in clinic.