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A nanocomposite of natural silica and ceria was synthesized to modify a screen-printed carbon electrode (SPCE) to develop an aptasensor to detect epithelial sodium channel (ENaC) protein in urine as a biomarker of hypertension. The method steps were the synthesis of natural silica-ceria nanocomposite using the hydrothermal method, obtaining of natural silica nanoparticles from the extraction of alkaline silica sand and ceria nanoparticles from cerium nitrate, modification of SPCE/natural silica-ceria, immobilization of aptamer through streptavidin-biotin, and detection of ENaC protein conc­entration. Box-Behnken’s design was employed to determine the optimal con­ditions of aptamer concentration (0.5 μg mL-1), streptavidin incubation time (30 min), and aptamer incubation time (1 hour), respectively. Differential pulse voltam­metry (DPV) characterization of the developed electrochemical aptasensor revealed that the [Fe(CN)6]3-/4- redox peak current increased from 3.190 to 9.073 μA, with detection and quantification limits of 0.113 and 0.343 ng mL-1, respectively. The method is proven as a simple and rapid method to monitor ENaC levels in urine samples.