Abstract: Objective To establish a stable， highsensitive detection technology of EGFR19 exon deletion mutation through combined restriction fragment length polymorphism（RFLP） and fragment analysis techniques. Methods Wide type DNA was digested to reduce the background. Fragment analysis was used to assess the length of DNA. The wild-type DNA was used to dilute mutant DNA to test the sensitivity of the method. Using this method， we detected the status of EGFR 19 exon in 42 non-small cell lung cancer（NSCLC） peripheral blood plasma.Results The mutant DNA diluted in wide-type DNA was used to test the sensitivity of the method and the highest sensitivity was 1∶1000（Mt∶Wt）. For the 42 plasma samples of NSCLC， 5 samples contained EGFR19 exon deletion mutation， with four cases 15bp deletion， 1 cases 24bp deletion.Conclusion We established a restriction enzyme digestion and fragment analysis based high sensitive method to detect plasma EGFR exon 19 deletion. The method can effectively identify EGFR19 exon deletion mutations in the peripheral blood.