Cellulose monoacetate/tetraethyl orthosilicate (CMA/TEOS) hybrid nanofibers were produced with different ratios via electrospinning and used for guanine oxidation analysis in the single strand deoxyribonucleic acid (ssDNA) molecules by electrochemical method. Nanofiber (NF) diameters for pure CMA dramatically decreased from between 2.4 mu, -306 nm to between 958-42 nm with addition of hydrochloric acid (HCl) catalyzer into the electrospinning solution. Uniform CMA nanofibers morphologies transform to more defect structures containing particular structures with the addition and increase of TEOS content in CMA electrospinning solution. Also, nanofibers' diameters range became more fluctuated form and ultrafine nanofibers (diameters below 100 nm) existed more in the nanofiber mat. Even though the melting point was seen at CMA nanofibers, melting points were not detectable in CMA/TEOS NFs since TEOS addition does not allow an appropriate crystallization. Thermal analysis results revealed that residual contents after TGA measurement in nitrogen atmosphere were gradually increased by increasing TEOS ratio in CMA/TEOS nanofibers. ssDNA molecules were immobilized on the as-spun nanofibers and differential pulse voltammetry (DPV) measurements were carried out to investigate the guanine oxidation in ssDNA. Guanine oxidation signal intensities decreased with the initial addition of TEOS to CMA nanofibers and increases again by increasing TEOS content in CMA/TEOS hybrid nanofibers and then gradually decreases again with increasing TEOS content. The prepared CMA/TEOS hybrid nanofibers could be a promising candidate as an electrode interface for genetic molecule detection via electrochemical methods.