We utilized localized Joule heating to ablate methoxy-poly (ethylene-glycol)-silane (mPEG-sil) modified on the p- region of an n+-p--n+ silicon nanobelt field-effect transistor (SNFET). SNFETs with selective modifications of 3- aminopropyltrimethoxysilane (APTMS) and NHS-biotin on the ablated region exhibited a faster sensing response rate and a higher sensitivity in real-time detection of Streptavidin (SA). Characterization of the ablated region via lateral force microscopy and the fluorescence image show that the ablation region occurs only in the p- region near the drain side and is believed to be a result of the impact ionization mechanism during Joule heating. Moreover, a bias of 20 V pulse voltage for 1 ms successfully ablates mPEG-sil and reduces the device off leakage current by 1 order after Joule heating. However, Joule heating with a pulse voltage larger than 20 V (1 ms) yielded an increase of device off leakage owing to damage to gate dielectrics during Joule heating. A comparison of real-time detection of SA between selectively and non-selectively modified chips shows that selectively modified ones exhibit a better limit of detection (LOD) that is one order lower than non-selectively modified ones, and a sensing response rate twice as fast as the non-selectively modified one for every target concentration.