Si1−xGex nanowire biosensors are attractive for their high sensitivity due to the large surface-to-volume ratio, high carrier mobility, and silicon compatibility. In this work, we study the effect of the thickness of the low-temperature Si (LT-Si) buffer layer on an insulator on the sensitivity of oxidized Si1−xGex nanowire samples with different Ge contents by increasing the Si buffer thickness from 20 to 60 nm. 3-Aminopropyltrimethoxysilane (APTMS) was used as a biochemical reagent. It was demonstrated that, with the proper Ge content and LT-Si buffer thickness, the sensitivity of the Si1−xGex nanowire is high and it can be further improved by Si1−xGex oxidation. This can be attributed to the reduction of the diameter to the nanometer order, which gives rise to an increased surface-to-volume ratio and further enhances the sensitivity of the biosensor.