Estrogens and estrogen-mimicking compounds in the aquatic environment are known to cause negative impacts to both ecosystems and human health. In this initial proof-of-principle study, we developed a novel vertically oriented silicon nanowire (vSiNW) array-based biosensor for low-cost, highly sensitive and selective detection of estrogens. The vSiNW arrays were formed using an inexpensive and scalable metal-assisted chemical etching (MACE) process. A vSiNW array-based p−n junction diode (vSiNW-diode) transducer design for the biosensor was used and functionalized via 3aminopropyltriethoxysilane (APTES)-based silane chemistry to bond estrogen receptor-alpha (ER-α) to the surface of the vSiNWs. Following receptor conjugation, the biosensors were exposed to increasing concentrations of estradiol (E2), resulting in a well-calibrated sensor response (R 2 ≥ 0.84, 1−100 ng/mL concentration range). Fluorescence measurements quantified the distribution of estrogen receptors across the vSiNW array compared to planar Si, indicating an average of 7 times higher receptor presence on the vSiNW array surface. We tested the biosensor's target selectivity by comparing it to another estrogen (estrone [E1]) and an androgen (testosterone), where we measured a high positive electrical biosensor response after E1 exposure and a minimal response after testosterone. The regeneration capacity of the biosensor was tested following three successive rinses with phosphate buffer solution (PBS) between hormone exposure. Traditional horizontally oriented Si NW field effect transistor (hSiNW-FET)-based biosensors report electrical current changes at the nanoampere (nA) level that require bulky and expensive measurement equipment making them unsuitable for field measurements, whereas the reported vSiNW-diode biosensor exhibits current changes in the microampere (μA) range, demonstrating up to 100-fold electrical signal amplification, thus enabling sensor signal measurement using inexpensive electronics. The highly sensitive and specific vSiNW-diode biosensor developed here will enable the creation of low-cost, portable, fielddeployable biosensors that can detect estrogenic compounds in waterways in real-time.