Non-small cell lung cancer (NSCLC) incited by epidermal growth factor receptor (EGFR) mutation makes up ∼85% of lung cancer diagnosed and death cases worldwide. The presented study introduced an alternative approach in detecting EGFR mutation using nano-silica integrated with polydimethylsiloxane (PDMS) polymer on interdigitated electrode (IDE) sensor. A 400 μm gap-sized aluminum IDE was modified with nano-polymer layer, which was made up of silica nanoparticles and PDMS polymer. IDE and PDMS-coated IDE (PDMS/IDE) were imaged using electron microscopes that reveals its smooth and ideal sensor morphology. The nano-silica-integrated PDMS/IDE surface was immobilized with EGFR probe and target to specify the lung cancer detection. The sensor specificity was justified through the insignificant current readouts with one-base mismatch and noncomplementary targets. The sensitivity of nano-silica-integrated PDMS/IDE was examined with mutant target spiked in human serum, where the resulting current affirms the detection of EGFR mutation. Based on the slope of the calibration curve, the sensitivity of nano-silica-integrated PDMS/IDE was 2.24E-9 A M-1 . The sensor recognizes EGFR mutation lowest at 1 aM complementary mutant target; however, the detection limit obtained based on 3σ calculation is 10 aM with regression value of 0.97.