In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations have emerged as important biomarkers in predicting the response to the EGFR tyrosine kinase inhibitors. The identification of these mutations is based on invasively obtained biopsy samples, which is not always acceptable in a clinical setting. The analysis of circulating tumor DNA or circulating tumor cells in the blood is an alternative approach but is often complicated, technique dependent, and time consuming. A noninvasive, readily available, diagnostic procedure with minimal preparation that provides immediate information on EGFR mutation status is desirable. We developed a novel core technology, Electric Field-Induced Release and Measurement (EFIRM) that can detect EGFR mutations directly from body fluids. We first demonstrated that EFIRM can detect EGFR mutations (exon 19 deletion and L858R) from saliva and serum of 22 NSCLC patients. And a blinded test on saliva samples from 40 NSCLC patient showed that EFIRM detected the exon 19 deletion and L858R with an area under the curve (AUC) of 0.94 and 0.96 respectively. For total 62 patients, the sensitivity of EFIRM in detecting L858R and exon 19 deletion in saliva is 84.2% and 91.7% respectively. And the specificity in detecting L858R is 95.3% which is the same as in exon 19 deletion. The amperometric currents EFIRM recorded was not affected by tumor burden, metastatic organ and staging. Finally, we investigate if digital PCR can be used to detect EGFR mutant DNA in saliva. The detection rate was 14.2% in exon 19 Del and 12.5% in L858R respectively. Our data indicated that EFIRM is accurate and user-friendly for the detection of EGFR mutations in the saliva and serum of NSCLC patients.