Abstract: Objective To validate the new digital PCR ( dPCR) -based assay platform for the detection of plasma-free DNA EGFR mutations in the patients with non-small cell lung cancer ( NSCLC)，and confrm its performance and clinical evaluation for future clinical application. Methods The samples with diferent concentrations of 19Del，L858R and T790M mutation provided by the reagent manufacturer were selected for the performance verification of a new platform based on multiple digital PCR, including precision , sensitivity，limit of blank and linearity test. The samples of 49 patients with NSCLC diagnosed in the Pneumology Department of Zhongshan Hospital, Fudan University from June 2019 to November 2020 were collected and analyzed by multiple dPCR and Super-ARMS. Chi-square test was used to compare the differences and the consistency of test results between the two groups. Results The accuracy of dPCR platform was good for the coefficient of variation among the three abundances of the three mutations ( L858R, 19Del, T790M) was less than 15%，which is in the line of the manufacturer's statement. Positive results were reported based on the three common mutations at different predicted detection limits (0.5%，0.1% and 0.05%). The limits of blank for T790M, 20ins and L858R mutations were 0.038 2, 0.000 and 0.053. The linearity was good in the range of 0.05% to 10% (0.05%, 0.1%, 0.5%, 1% and 10%). The R2 in the linear regression equation of the measured value withthe expected percentage were 0.997 7, 0.995 4 and 0.998 4, respectively (P<0.01), indicating significant correlation. For the results of 49 clinical samples , the overall agreements between the new mult iplex dPCR platform and the Super-ARMS platfom in the detections for S768I, G719X, 19Del, T790M, 20ins and L858R mutations were 100%， 100%，100%, 97.96%, 93.62% and 89. 80%，respectively. The Chi-square test showed that no significant diference was found between the results of L858R(X2 = 0.425 ,P>0.05), T790M(x2 =0.089 ,P>0.05), 19Del(x2 =0,P>0.05)and 20ins (x2=0.211, P>0.05 ). Conclusion The new multiplex dagital PCR platform showed good performance in detecting common mutations of EGFR in free DNA, which may be tentatively considered as an advantageous method for detecting mutation abundance, thus could provide laboratory basis for supporting tumor precision therapy .